Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 8th International Conference on Tissue Science and Regenerative Medicine Singapore.

Day 1 :

Keynote Forum

Claire Henchcliffe

Weill Cornell Medical Center, USA

Keynote: Regenerative treatments for Parkinson’s disease: How far can stem cells take us?

Time : 09:00-09:40

Conference Series Tissue Science Congress 2017 International Conference Keynote Speaker Claire Henchcliffe photo
Biography:

Claire Henchcliffe serves as the Director for the Weill Cornell Parkinson’s Disease & Movement Disorders Institute in New York, Vice Chair for Clinical Research and Associate Professor in Neurology, New York at Presbyterian Hospital/Weill Cornell Medical Center, New York, USA. She has completed her Doctorate degree at Oxford University, UK, followed by Post-doctoral Genetics and Neuroscience research at the University of Cambridge, UK and the University of California at Berkeley, USA. She has completed her Medical training at the College of Physicians and Surgeons of Columbia University in New York. She is a Fellow of the American Academy of Neurology and the American Neurological Association and a Member of the Movement Disorders Society and the Parkinson’s Study Group. She has published and lectured widely on Parkinson’s disease.

Abstract:

Rapid advances in stem cell technology have resulted in promise for a neurorestorative approach for treating Parkinson’s disease (PD), a disabling neurodegenerative movement disorder. Parthenogenetic neural progenitor cells are in early clinical testing and several groups, including ours, now seek to examine the effects of transplanting dopamine cells derived from either hESC or iPS cells. In light of these current efforts, it is important to understand outcomes of previous attempts at cell replacement. Previous transplant studies have most commonly focused upon human fetal tissue, although autologous adrenal tissue transplants and retinal pigmented epithelial cells have been tested and will be reviewed. Open label studies of human fetal tissue allotransplantation starting in Lund, Sweden in 1987 paved the way for multiple clinical trials, including two randomized, double blinded, sham surgery controlled clinical trials of bilateral tissue transplant in PD. However, despite this rich history, there is a dearth of data on very long term outcomes. We have therefore examined five surviving participants from the NIH-funded, randomized, double blinded, sham surgery controlled clinical trial of fetal ventral mesencephalic tissue transplant in advanced PD undertaken at the University of Colorado. These patients underwent surgery in 1997-1998 and were examined up to 36 years’ PD duration. Video-recorded motor examinations and Parkinson’s Kinetigraph™ accelerometry-based continuous monitoring demonstrated motor signs consistent with surviving graft tissue as measured by 11C-PE2i PET imaging. In particular, we observed an unexpectedly high level of motor function in two subjects at 28 years and 35 years PD duration. However, non-motor features and non-dopa responsive symptoms were prominent, including sleep disorders, dysautonomia and imbalance. In summary, at very long term follow up 17-18 years post-transplant, there is evidence of graft survival with clinical heterogeneity between subjects likely reflecting heterogeneous graft as well as underlying differences between PD patients.

Keynote Forum

Nadia Benkirane-Jessel

Inserm - French National Institute of Health and Medical Research, France

Keynote: Combined therapeutic medical device and stem cells for regenerative nanomedicine

Time : 09:40-10:20

Conference Series Tissue Science Congress 2017 International Conference Keynote Speaker Nadia Benkirane-Jessel photo
Biography:

Nadia Benkirane-Jessel is a Research Director and Head of the Osteoarticular and Dental Regenerative Nanomedicine laboratory at INSERM (French National Institute for Health and Medical Research), France. She has received her PhD from University Louis Pasteur, France for the work on development of pseudopeptides as synthetic vaccines. She has then held a Postdoctoral position in collaboration with the Institut Pasteur, France, working on immunotherapy HIV and another Postdoctoral position on the application of modified peptides as vaccines against FMDV (Plum Island Animal Disease Center, ARS, USDA, Greenport, USA). She has joined the INSERM U595 in 2002 as a Post-doctorate and received a Diploma to direct the research (HDR) in 2004. She possesses expertise in diverse fields of molecular and cellular biology, immunochemistry, tissue engineering and biomedical engineering. In the last 10 years, she focused her research on the bio-functionalization of multilayered polyelectrolyte architectures with emphasis on the use of these architectures to induce specific cellular responses and gain control over cell proliferation and differentiation. She has 138 peer-reviewed publications in high impact factor journals, 5 chapter reviews and 5 international patents and is a regular referee for a number of scientific journals.

Abstract:

In our group we explore a new generation of smart living implants combining not only active therapeutics but also stem cells, as a novel strategy to regenerate stabilized cartilage and avoid prosthesis by achieving regeneration of its subchondral bone foundation, requirement which is failing today in the clinic. In our group, a unique nanotechnology strategy is used to entrap, protect and stabilize therapeutic agents into polymer coatings: Nanoreservoirs, covering nanofibers of implantable nanofibrous membranes for bone and cartilage regeneration. Upon contact with cells, therapeutic agents become available through enzymatic degradation of the nanoreservoirs. As cells grow, divide and infiltrate deeper into the porous membrane, they trigger slow and progressive release of therapeutic agents that, in turn, stimulate further cell proliferation. The nanoreservoirs technology enables to reduce the quantities of required therapeutic agent (compared to soaked membranes for instance) thereby reducing costs.

Keynote Forum

Tanongsak Panyawirunroj

Asia Cosmetic Hospital, Thailand

Keynote: Minimal invasive TANONGSAK technique for reduction malarplasty

Time : 10:20-11:00

Conference Series Tissue Science Congress 2017 International Conference Keynote Speaker Tanongsak Panyawirunroj photo
Biography:

Dr. Tanongsak Panyawirunroj is a Founder, a Chairman, and the principal surgeon at Asia Cosmetic Hospital Thailand, The Best Plastic Surgery in Thailand. Dr. Tanongsak Panyawirunroj specializes in Maxillofacial surgery, Breast augmentation, Face Change – from male to female, Rhinoplasty, Liposuction, Sex Change – from male to female and etc. He has many certifications for various domains such as: micro-vascular surgery, plastic surgery, maxilla-facial surgery, aesthetic surgery and pediatric surgery. The doctor is also a member of the International Society of the Aesthetic Plastic Surgery. Dr. Tanongsak Panyawirunroj never thought of any field other than medicine since childhood. He chose as his Alma Mater the Siriraj Hospital Medical College of Mahidol University (Bangkok, THAILAND). He has earned the degree of Doctor of Medicine in 1998. Furthermore, he has been winning and earning many more awards, trophies and certificates. The latest award was The Best Manager Awards 2015, Medical Sphere (SOCRATES AWARDS  2015)  by Europe Business Assembly. And the recent reputation was being as Honorable speaker and Chairman for Plastic Aesthetic Surgery Conference 2016, Toronto, Canada.

Abstract:

Background

Southeast Asian women prefer oval shape facial contour. To achieve this goal, there are a lot of procedures to reshape the facial skeleton. Reduction malarplasty is a common operation. Although multiple technique have been developed for reduction malarplasty. This study presents a new less invasive TANONGSAK technique for reduction malarplasty.

Methods

Between January 2015 and December 2015, we applied TANONGSAK technique for reduction malarplasty in 38 patients. TANONGSAK technique was performed osteotomy site at zygomatic arch with 12 mm in length preauricular incision and at Zygomatic body with 25 mm in length intraoral incision by a reciprocating saw. Out site-in Closed reduction was performed to reposition of malar bone complex. Internal fixation was not required.

Results

The patients were followed up for 5 to 183 days postoperatively (mean 39 days). 94% of patients (36 patients) had satisfactory aesthetic results. The facial contour reduction was accomplished 0.1%-13.79% (mean 2.46%) in size reduction. The operative time in each case was less than 60 minutes. The mean hospital stay was 1.1 day (1-2 day) and patients required recovery period 2-14 days (mean 8.7 days) .2 of patients developed temporary inferior orbital nerve injury. No facial nerve injury and no any other postoperative complications.

Conclusion

Minimal invasive TANONGSAK reduction malarplasty is a preferable technique. This technique provides multiple advantages, including simple manipulation, less invasive, short incision, no internal fixation, good stability, achieved aesthetic results, short operative and recovery time, and less complications. 

  • Cell & Organ Regeneration | Tissue Repair & Regeneration | Advances in Stem Cell | Rejuvenation- Fight Aging
Location: Seletar
Speaker

Chair

Alain Chapel

IRSN- Institute of Radioprotection and Nuclear Safety, France

Speaker

Co-Chair

Nelson Pinto

University of the Andes, Chile

Speaker
Biography:

Michael H Heggeness has completed his PhD at UC San Diego in Membrane Biology and a Post-doctorate at Rockefeller University in Virology. He has received his MD from the University of Miami. After his Residency in Orthopedic Surgery, he has completed a Fellowship in Spine Surgery at the University of Toronto. He has then joined the Faculty at Baylor College of Medicine where he became Chairman of Orthopedic Surgery in 2004. He then moved to take the chair at University of Kansas in Wichita in 2013. He has 84 publications and 4 issued patents to his credit. His interest has centered on intraosseous nerves and nerve derived stem cells.

Abstract:

Preliminary evidence from our laboratory has documented a large population of quiescent stem cells within peripheral nerves. In response to nerve injury, or stimulation with the cytokine BMP2, these cells proliferate and generate populations of pluripotent stem cells, expressing Sox2, Klf4, Oct4 and c-Myc (verified by double stain immunohistochemistry and by real time PCR). These 4 markers are the transcription factors that confer embryonic pluripotency (Cell 126: 663, 2006). We call them Nerve Derived Pluripotent Stem cells, or NEDAPS cells. The cells are readily induced to form tissues from all 3 germ layers. We hypothesize that these cells are central to a previously unknown universal pathway for tissue repair. Nerves are nearly ubiquitous in the body, from the cornea of the eye to every hair follicle. Thus, we believe that nerve injury, and the consequent proliferation of these stem cells, is occurring following essentially any injury. We propose that this is a previously unknown universal pathway for healing

We will show data documenting the induction and successful culture pluripotent cells from three mammalian species, and demonstrate their directed differentiation into osteoblasts, endothelial cells, primitive neural cells, definitive endoderm and fibroblasts as demonstrated by morphology, immunohistochemical staining and RT-PCR.

Recent progress has been stimulated by the discovery that induced pluripotent stem cells (iPCs), can be created from fully differentiated cells using retrovirus vectors (Cell 126: 663,2006).  Such iPCs are widely studied as possible sources of cells for the treatment of human disease. This work has almost entirely been focused on a search for cures and treatments for specific diseases, and has been hampered by issues of malignant transformation of iPCs, and by immune rejection of “non-self” cells. We are aware that previous claims to successful identification of cells with universal differentiation from non-gonadal adult tissue have resulted in some well publicized scandals, involving fabricated data. These scandals have understandably created a skeptical audience for us. Such pluripotent stem cells are thought not to exist in adult animals (SciON 311: 814 2006), and until our recent discovery, we believed the same. Confidence in our admittedly unprecedented ideas is provided by information from other species. It is known that a salamander can re-grow an entire arm after amputation, but that ablation of the nerve stump will block the regeneration. Similarly, a starfish will regenerate an entire arm as well, but similarly, will not do so if the nerve supply is ablated (Kumar and Brokes Trend. Neurosci 2012 p691)

We propose that this new knowledge will also explain the puzzling and vexing clinical problem of impaired wound healing experienced by severely diabetic patients and victims of leprosy. We suggest that the associated clinical neuropathies explain this. The other implication of this discovery is that we may now have a new opportunity for individual specific “self-to-self” stem cell treatments, based on patient specific peripheral nerve harvest.

 

Speaker
Biography:

Susan Chubinskaya is an Associate Provost for Faculty Affairs at Rush University and Vice-Chair, Research and Faculty Development, Department of Pediatrics. She also holds joint appointments as Professor in the Departments of Internal Medicine and Orthopedic Surgery at Rush University Medical Center. She is an internationally recognized expert in the field of cartilage repair/regeneration, especially in post-traumatic and degenerative osteoarthritis. She has published more than 90 peer-reviewed manuscripts, 12 book chapters and more than 220 peer-reviewed abstracts.

Abstract:

Statement of the Problem: Osteoarthritis (OA) is the most common cause of disability with one in three adults of working age having arthritis-attributable work limitations. In at least 12% of patients with symptomatic OA, the cause is joint injury that progressed over time to post-traumatic OA. Human adult articular cartilage has a limited innate ability to regenerate. Currently, no methodology is able to restore native structure and function of hyaline cartilage, though various approved surgical procedures lead to temporarily improved clinical outcomes. Furthermore, it is unclear whether the restoration of native cartilage structure is necessary for symptomatic improvement. In this presentation we will discuss new experimental biologic developments in the field of cartilage regeneration.

Methodology & Theoretical Orientation: We will provide an overview of new technologies tested in vitro and in vivo in animal models and in Phase-I clinical studies. We will also comment on existing clinical trials and discuss potential therapies for cartilage regeneration.

Findings: New technologies aimed to regenerate cartilage usually involve cells growth and differentiation factors, a scaffold or graft, or combination therein. When addressing the question of cartilage regeneration it is critical to consider integration with surrounding cartilage tissue and subchondral bone. Cell sources for cartilage regeneration have included bone marrow mesenchymal stem cells (BM-MSCs, MSCs), umbilical cord cells, embryonic stem cells, human placental membrane and adipose derived MSCs, to name a few. Some approaches, like osteochondral grafts and minced cartilage products, have a benefit of the existing native matrix structure; though they are expensive and have low availability. To address regeneration of the osteochondral unit the focus has shifted to acellular scaffolds, preferably heterogeneous, that combines two distinct layers corresponding to the cartilage and bone to enable simultaneous regeneration of both tissues. One example of such scaffold that has been extensively tested in our laboratory and in animal models and human clinical trials is Agili-C (CartiHeal, Israel). This scaffold consists of a natural crystalline aragonite, derived from corals, to which hyaluronic acid is added. It showed a great ability to induce regeneration of chondral and osteochondral lesions and attract chondrocytes and stems cells to fill the defect area. We will also present evidence for biologic mechanism based therapies to have a potential to halt cartilage degeneration and stimulate repair.

Conclusion & Significance: A number of new and exciting technologies are being developed for cartilage regeneration. However, one of the biggest challenges is the translation into the clinic.

Wilson Wang Ee Jen

National University of Singapore, Singapore

Title: Tissue engineering and 3D printing of meniscal, tendon and musculoskeletal structures

Time : 11:55-12:15

Speaker
Biography:

Wilson Wang is the Head of the Department of Orthopedic Surgery at the Yong Loo Lin School of Medicine, National University of Singapore (NUS) and also Head of Department and Head of Division of Hip and Knee Surgery at National University Hospital (NUH), Singapore. He specializes in a wide range of hip and knee treatments and operations, including primary, revision and complex total joint replacement surgery of the knee and hip; other lower limb joint reconstructive operations (e.g., osteotomies); arthroscopic surgery for hip and knee including labral repairs, ligament reconstructions, meniscal repairs and cartilage and scaffold reconstructions and complex and advanced joint surgery such as meniscal transplants, partial knee replacements and 3D/robotic guided surgery. He is the current Chairman of the Hip Section of Asia Pacific Orthopedic Association (APOA) and of the Asia Pacific Hip Society (APHS).

Abstract:

Additive manufacturing and scaffold-building for tissue-engineered biological structures hold much potential promise for future therapeutic and clinical applications. Established techniques such as electrospinning, solvent-casting, salt leaching, solvent low temperature gelation and critical point drying have all been used in various ways to create bioscaffold structures that can potentially be used in tissue replacement situations. However such techniques mainly generate structures that are non-directional or randomly arranged in internal architecture, and they tend to lack anisotropic properties that are beneficial in specific clinical applications.

 

With the advent of additive manufacturing (AM) and 3-dimensional (3D) printing, a new range of possibilities has emerged, based on the technologies’ capabilies in rapid prototyping, customizable morphology, specification of internal microstructures and enhanced resolutions. These new techniques however also have specific limitations with regards to range of printable materials, handling difficulties of solvents and other technical considerations. Early applications were thus limited to creation of structures for surgical guides, and tissue or organ models for complex surgical planning. More recent developments have enabled high resolution 3D printing of tissue scaffold structures using biocompatible materials, and viable cellular printing is now a reality in the laboratory setting. Musculoskeletal tissues such as cartilage, meniscus, tendons and bone are particularly suitable as targets of such technologies, due to their specific functions and structural properties, and examples of potential clinical applications for these novel techniques and approaches will be highlighted and discussed.

Speaker
Biography:

Fumio Arai is a Professor of Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University. In 2002, he moved to School of Medicine, Keio University, Tokyo and investigated the molecular mechanism of the regulation of hematopoietic stem cells (HSCs) in their niche. His research interest is in studying the mechanisms of the cell fate regulation of HSCs at the single cell level for the establishment of the system that is able to expand HSCs.

Abstract:

Repeated cell divisions and aging impair stem cell function. However, the mechanisms by which this occurs are not fully understood. Here, we show that POT1a, a component of shelterin complex, improves hematopoietic stem cell (HSC) activity under stress and during aging. We found that POT1a was highly expressed in HSCs, yet this expression declined with age. POT1a knockdown in HSCs increased DNA damage response (DDR) and inhibited self-renewal. Conversely, POT1a overexpression or treatment with exogenous POT1a protein prevented DDR, maintained HSC self-renewal and rejuvenated the activity of aged HSCs. Notably; we found that POT1a negatively regulated mTOR and Raptor expression and POT1a transduction prevented the expression of oxidative phosphorylation-associated genes and reduced the production of reactive oxygen species, indicating a novel non-telomeric function of POT1a in HSC maintenance. Furthermore, exogenous POT1 protein treatment also maintained human HSC activity. Collectively, these results show that POT1a/POT1 can be used to expand HSC numbers ex vivo.

Shrikant L. Kulkarni

Kulkarni Clinic, India

Title: Rejuvenation approach to treat chronic kidney diseases

Time : 12:35-12:55

Speaker
Biography:

Shrikant L Kulkarni has completed his MS General Surgery in 1975 from B J Medical College in India and has completed his MBBS from Government Medical College Miraj. Since 1971, he has been working at several government hospitals like the Wanless Hospital Miraj, General Hospital Sangli, Sassoon Hospital Pune and multispecialty hospitals like Ruby Hall Clinic and Jehangir Nursing Home. He is currently working at his own clinic in India since more than 35 years.

Abstract:

Rejuvenate means make young or youthful again to an original new state by natural healing process. Kidney loses its functionality due to age, disease, damage or congenital defects. The therapeutic repair by self-healing process is the rejuvenation, regeneration or replacement. The current treatment approach includes transplantation of the kidney, tissue engineering cell therapy and gene therapy. In cell based therapy the exogenous material is used in unwilling failed organ forcefully but uncertainty about survival and adaption due to toxic environment in the host tissue. Creation of friendly environment is unsolved problem in cell based therapy. The main root cause for chronic kidney diseases (CKD) is fibrosis; to treat fibrosis is through the body’s natural process of healing. Body can be repaired if fibrosis dissolved which restore blood circulation, elasticity of arteries and improve inflammatory immune system which creates the healthy microenvironment for regeneration of a damaged tissue. Rejuvenation is the self-repair self-directed and motivated autonomous process which is ideal treatment for the failed organ with recovery with physiological function. This endogenous natural process of healing replaces the young cells which are having strong stress tolerance for tissue survival. The aim of this article is to discuss the use of regenerative science self-organ regeneration by dissolving the fibrosis in renal parenchyma and stimulate in damaged tissues, which can be treated by Artificially Producing Hydronephrosis (APH treatment) method. The following steps are involved in this treatment: (1) The pelvic-ureteric junction (PUJ) is blocked to create hydronephrotic condition, (2) Due to increased back pressure the fibrosed renal parenchyma is dissolved, and (3) Remove the artificial block at PUJ causing back pressure reduction. This gives a healthy environment to regenerate the normal renal tissue from the renal stem cell niches which are present around the kidney cortex. The APH treatment makes use of the power of regeneration existing in our body. Theoretically the prognosis states that the stem cells niches between renal capsule and the cortex will start regeneration of normal renal parenchyma.

  • Bone Tissue Engineering | Scaffolds in Regenerative Medicine | Cancer Therapy
Location: Seletar

Session Introduction

Matteo Moretti

IRCCS Galeazzi Orthopedic Institute, Italy

Title: Advanced 3D vascularized in vitro models of human bone and muscle to study tumor cell extravasation

Time : 13:55-14:15

Speaker
Biography:

Matteo Moretti is the Director of the Cell and Tissue Engineering Lab at Galeazzi Hospital in Milan, Italy and of the Regenerative Medicine Technologies Lab at EOC in Lugano, Switzerland. His main research interests lie within micro and meso-scale advanced cell culture technologies. He has developed multiscale bioreactor systems from design to fully working prototypes, aimed at up-scalable, automated platforms as a key to more viable advanced therapies. Furthermore, he has worked on the application of different physicochemical cues to engineered vascularized physiological and pathological tissues, with concern to human primary in vitro 3D model systems aimed at translational applications and as novel tools for biology research. He is a Treasurer of the Tissue Engineering and Regenerative Medicine Society European chapter (TERMIS-EU). He has authored more than 60 papers on international peer-reviewed journals and has co-founded two biotech start-ups.

Abstract:

Cancer metastases cause 90% of cancer deaths and affect different organs, depending on the tumor, e.g., breast cancer metastasizes to bone but not to skeletal muscle. Extravasation is the last critical step of metastatic cascade before organ colonization and for its investigation; standard in vitro models are oversimplified, while in vivo models are analytically limited and present species-specific differences in pathological mechanisms. Thus, we generated innovative in vitro models for the study of breast cancer cell (BCC) extravasation. Our models are based on 3D gels embedding co-cultures of human bone, muscle and vascular cells. They can be either microscale based on microfluidics or mesoscale, exploiting ad-hoc designed supports. BCCs injected into microvascular networks of our models extravasated more towards bone model, compared to control and to skeletal muscle model (56.5±4.8% vs. 14.7±3.6% vs. 8.2±2.3%) although permeability of the bone endothelium was lower. Furthermore, adenosine addition to the bone model decreased extravasation (12.7±2.8% vs. 56.5±4.8%) and the supplementation of a specific adenosine inhibitor in the muscle model increased BCC extravasation (32.4±7.7% vs. 8.2±2.3%). Furthermore, with these models we demonstrated the key role of Talin-1 protein in the extravasation process. We also generated the first 3D in vitro mesoscale models of metabolically active human bone and we have biofabricated a 3D human vascularized skeletal muscle environment, which not only incorporates a physiological muscle-specific vascular network, but also includes muscle-supporting fibroblasts recapitulating the structure of the endomysium. In conclusion, our 3D in vitro human models, vascularized and organ-specific allowed us to replicate the process of extravasation of breast cancer cells and to investigate its basic biological mechanisms, thanks to the control on the microenvironment and to the high resolution of analytical methods.

Gautam Sethi

National University of Singapore, Singapore

Title: Oncogenic transcription factor STAT3 as a target for cancer prevention and therapy

Time : 14:15-14:35

Speaker
Biography:

Gautam Sethi has completed his Postdoctoral training at University of Texas MD Anderson Cancer Center and joined Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore in 2008 as an Assistant Professor and was promoted to Associate Professor in 2015. The focus of his research over the past few years has been to elucidate the mechanism(s) of activation of oncogenic transcription factors such as NF-kB/STAT3 by carcinogens and inflammatory agents and the identification of novel inhibitors of these proteins for prevention of and therapy for cancer. The findings of his research work have so far resulted in more than 150 scientific publications in high impact factor peer reviewed journals. He currently serves as an Academic Editor for PLOS One, Editorial Board Member of Scientific Reports and ad-hoc Reviewer for several other international journals. 

Abstract:

STATs comprise a family of cytoplasmic transcription factors that transmit signals, mediate intracellular signaling usually generated at cell surface receptors and transmitted to the nucleus. Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human tumors, including blood malignancies (leukemias, lymphomas and multiple myeloma) as well as solid tissues (such as head and neck, breast, lung, gastric, hepatocellular and prostate cancers). There is a strong evidence to suggest that aberrant STAT3 signaling promotes development and progression of human cancers by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion and metastasis. However, the development of novel drugs for the targeting STAT3 that is both safe and efficacious remains an important scientific and clinical challenge. This study present the data that shows that novel small molecule inhibitors of STAT3/JAK2 pathway can suppress the expression of genes involved in cancer initiation and promotion both in vitro and in vivo.

Yvonne Tay

National University of Singapore, Singapore

Title: A microRNA-638/ferritin gene: Pseudogene network regulates iron storage in prostate cancer

Time : 14:35-14:55

Speaker
Biography:

Yvonne Tay has received her PhD in 2008 from the National University of Singapore and Genome Institute of Singapore (GIS). Her PhD work, which was supported by an A*STAR Graduate Scholarship led to seminal contributions to our understanding of the mechanisms of microRNA function. She was awarded the 2009 Philip Yeo Prize for Outstanding Achievement in Research by A*STAR in recognition of these breakthrough discoveries. After a two year Postdoctoral stint at A*STAR, she subsequently received a Special Fellow award from the Leukemia Lymphoma Society to continue her Postdoctoral training at Harvard Medical School and Beth Israel Deaconess Medical Center. Her postdoctoral research in the Pandolfi Lab led to the discovery that protein-coding transcripts can co-regulate the tumor suppressor PTEN by competing for shared microRNAs. She has recently commenced her new appointments as an Assistant Professor in the Department of Biochemistry and Junior Principal Investigator at the Cancer Science Institute of the National University of Singapore in September 2014.

Abstract:

MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally modulate gene expression by binding to miRNA response elements (MREs) on target transcripts. Aberrant expression of miRNAs results in the deregulation of tumor suppressors and/or oncogenes. Iron is an essential metal known to play critical roles in various cellular processes. Deregulated iron homeostasis tilts the systemic iron balance, leading to various human pathologies, including cancer. However, little is known about miRNAs in the regulation of iron storage. In this study, we characterize miRNA-638 as a crucial player in iron storage in prostate cancer, which is the second leading cause of cancer death in men worldwide. MiRNA-638 targets ferritin heavy chain, FTH1 and several of its pseudogenes to promote tumor growth, suggesting the potential involvement of a deregulated competing endogenous RNA (ceRNA) network in pathogenesis. Our results indicate that miRNA-638 could be an oncomiRNA in prostate cancer; hence it is a potential therapeutic target.

Sang-Bing Ong

Duke-NUS Medical School, Singapore

Title: Mapping cardiac progenitor cell fate via the mitochondria

Time : 14:55-15:15

Speaker
Biography:

Sang-Bing Ong has completed his PhD at University College London, UK in the year 2010. He has then completed his Postdoctoral studies at University of California, USA in 2012. He has worked as an Adjunct Lecturer in Biomedical Engineering in Universiti Teknologi Malaysia till 2015. Currently he is working as an Assistant Professor under Cardiovascular and Metabolic Diseases Program in Duke-NUS Medical School, Singapore.

Abstract:

Studies have documented that the adult heart contains a pool of CPCs that are clonogenic, self-renewing and multipotent. These cells are thought to exist in the heart to facilitate growth during adolescence and to provide a mechanism for minor repair and ongoing cell turnover within the adult heart. The CPCs have been shown to have therapeutic potential. To be effective in repairing the heart, the infused CPCs must successfully engraft, proliferate and differentiate into cells of the cardiac lineages. Although many studies have begun to investigate the signaling mechanisms involved in these processes, there are still significant gaps in our knowledge regarding the differentiation process of CPCs. Most importantly, little or no attention has been given to the alterations in mitochondria and redox status during differentiation of the CPCs. To transition from a non-contracting progenitor cell requiring little energy to a beating cardiac myocyte requires development of an energetic infrastructure that is capable of supporting the high metabolic demands of the myocyte. Thus, when a CPC commits to a myocyte lineage it must undergo substantial expansion, reprogramming and reorganization of its mitochondria, but how these processes are regulated in CPCs are currently unknown. This talk will shed light into the processes regulating mitochondrial maturation in CPCs during differentiation.

Emmanuel Mukwevho

North West University, South Africa

Title: Adiponectin regulation of AMPK on oleanolic acid treated Sprague Dawley rats

Time : 15:15-15:35

Speaker
Biography:

Emmanuel Mukwevho has completed his PhD in 2010 from University of Cape Town, South Africa in Anatomy and Cell Biology. He is an Associate Professor of Biochemistry at North West University, South Africa. He has published both nationally and internationally in reputed journals and his specialty is in Obesity and Diabetes where he leads the Diabetes & Obesity Therapeutics Research group at North West University.

Abstract:

AMPK is known to control glucose and lipid metabolism, two main candidates critical in the development of type-2 diabetes (T2D). Studies have shown that AMPK can be activated by adiponectin. Patients suffering from T2D are known to have low adiponectin concentration in their blood plasma. In this study we have assessed one of the anti-diabetic compounds Oleanolic Acid (OA), if it could produce desirable effect in up-regulating adiponectin concentration and the subsequent regulation of AMPK. Sprague Dawley rats were fed with high fructose diet (HFD) to induce T2D and the rats that developed insulin resistance were considered as diseased, they were then treated with OA. Analysis of adiponectin concentration in blood plasma was done, AMPK gene expression and subsequent genes that play vital role in glucose and lipid metabolism (GLUT-4 and CPT-1) in skeletal muscle tissue was also performed. The results showed 1.19 folds increase in blood plasma adiponectin concentration after OA administration. Furthermore AMPK gene expression showed 3.98 fold increase and GLUT-4 gene expression was increased with 1.5 fold whereas CTP-1 gene expression was increased with 1.59 folds. These results clearly indicate that OA produced good effects in ameliorating insulin resistance since it was able to up-regulate all the genes and adiponectin concentration which are well known to be abnormally suppressed in a situation of T2D. In conclusion this study further confirms that OA can be used as an effective therapeutic agent to ameliorate T2D and suggest that OA’s mechanism of action could be through AMPK pathway.

Speaker
Biography:

Nafiseh Baheiraei has completed her PhD in Tissue Engineering at Tehran University of Medical Sciences in Iran. She has been working as an Assistant Professor since 2015 at Faculty of Medical Sciences, Tarbiat Modares University in Iran. The main focus of her research is on bone and cardiac tissue engineering. More specifically, she is interested in novel biomaterials for tissue engineering and regenerative medicine applications. Currently she focused on better techniques for fabricating new scaffolds containing electroactive moieties including conductive polymers and nanomaterials.

Abstract:

Statement of the Problem: Bone defects are a fundamental public health issues and are the leading cause of morbidity and disability in elderly patients. Tissue engineering techniques provide a new method of regenerating damaged or diseased bone tissue. The purpose of this study was to develop and characterize collagen (COL) and collagen/beta tricalcium phosphate (COL/βTCP) scaffolds with a βTCP/collagen weight ratio of 4 using a freeze drying method.

Methodology & Theoretical Orientation: Physicochemical and biological characteristics of the samples were evaluated. The capability of the prepared scaffolds for vascularization and differentiation of mouse mesenchymal stem cells (MSCs) were also investigated.

Findings: A microporous structure with large porosity (95-98%) and appropriate pore size (120-200 µm) was observed for prepared samples. COL/βTCP scaffolds had a much higher compressive modulus than pure COL, while remaining porous with obvious flexibility. Apatite formation was confirmed by immersing the composite scaffold in simulated body fluid for 7 days. ALP assay revealed that porous COL/βTCP can effectively activate the differentiation of MSCs into osteoblasts. Composite scaffolds also promoted vascularization with good integration with the surrounding tissue.

Conclusion & Significance: Introduction of βTCP powder into the porous collagen matrix effectively improved the mechanical and biological properties of the collagen scaffolds, thereby making them potential bone substitutes for enhanced bone regeneration in orthopedic and dental applications.

Speaker
Biography:

Neelima Mishra has completed her PhD from Banasthali University, India. She is the Assistant Professor of Sanskriti University Mathura, India. She has published more than 15 papers in reputed journals, written two books and has been serving as an Editorial Board Member of national journal. Her research work mainly focuses on syntheses and biological potent of Schiff base metal complexes of La(III), Ce(III) and Th(IV) and syntheses of natural and synthetic polymers. She is the Member of India Science Congress, Chemical Teacher Association, Indian Chemical Society, Royal Society of Chemistry and American Chemical Society.

Abstract:

Metal-based antioxidants has received effort in order to identify the compounds having high free radical scavenging capacity related to various disorders and diseases associated with oxidative damage due to reactive oxygen species (ROS). Two mononuclear Th(IV) complexes were derived from 2,3–dihydro–1H–indolo[2,3–b]phenazine–4(5H)–ylidene)benzothiazole–2–amine (L1) and 3–(ethoxymethylene)–(2,3–hihydro–1H–indolo[2,3–b]phenazine–4(5H)–ylidene)benzothiazole–2–amine (L2) with properties of pharmacologically interest. The compounds were characterized by elemental analyses, molar conductance, magnetic susceptibility measurements, FTIR, UV-Vis, 1H NMR, TGA and XRD studies. In both complexes 2:1 ligand-to-metal ratio has been observed. Ligands and metals complexes showed antimicrobials and antioxidants activities. Antioxidant property is shown by DPPH and H2O2 Scavenging methods. Antimicrobial activities against E. coli, S. aureus bacteria and C. tropicalis, A. niger by test tube method.

  • Poster Presentations
Location: Seletar

Session Introduction

Elena A Gubareva

Kuban State Medical University, Russia

Title: Biophysical methods for scaffolds evaluation in rats
Speaker
Biography:

Elena A Gubareva has completed her MD and PhD from Kuban State Medical University in Russia. She works as Laboratory Head in International Research, Clinical and Education Center of Regenerative Medicine, Kuban State Medical University, Russia. She has published more than 80 papers in reputed journals both in Russia and abroad. 

Abstract:

Morphological and molecular methods are traditionally used to evaluate the biocompatibility of tissue engineered scaffolds in regenerative medicine. Recently it has become possible to apply biophysical approaches like chemiluminescence (CHL). Free radical oxidation reactions are well-known for biological processes regulation; the study of the intensity of this process in native and recellularized tissues and decellularized matrices can serve as a criterion for quantifying the viability of cellular structures and to evaluate quality of tissue decellularization and recellularization. CHL in heart, lung and diaphragm tissues were carried out with the use of the hardware-software Chemoluminometer Lum-5773 (PowerGraph 3.x Professional). Test tissue diameter was 6.0±0.1 mm, thickness 4.0±0.2 mm. All samples of native and recellularized tissues demonstrated a sharper increase, followed by an accelerated decrease in H2O2-induced CHL flare compared to decellularized ones. The study showed that CHL index is always significantly higher in native tissues compared to decellularized ones: 3.3 times in the heart (p=0.009), 8.9 times in the lung (p=0.014) and 2.0 times in the diaphragm (p=0.010). Higher CHL index is characteristic of the recellularized tissues, which exceed the native ones: 26 times in the lung (p=0.015) and 6.7 times in the diaphragm (p=0.014). It allows controlling the efficiency of decellularization and recellularization in different organs with the help of H2O2-induced CHL. Thus, the intensity of CHL of native and recellularized heart, lungs and diaphragm tissues significantly differs from the indices of CHL of decellularized ones, which is characterized by the regularity of the change in this index, which increases reliably in the following comparative series: Decellularized tissues

Speaker
Biography:

Elena A Gubareva has completed her MD and PhD from Kuban State Medical University in Russia. She works as Laboratory Head in International Research, Clinical and Education Center of Regenerative Medicine in Kuban State Medical University, Russia. She has published more than 80 papers in reputed journals both in Russia and abroad.

Abstract:

The main reason for diaphragm pathology is muscular damage: The congenital or acquired hernia or failure of innervation, eventration of the diaphragm, diaphragmatic paralysis or pacing. Recent advantages in tissue engineering have opened new prospects for the replacement of the skeletal muscle, especially diaphragm. It is also important for tissue engineered muscle to provide a patch of functional skeletal muscle with no atrophy and with a low risk of infection. Several routine surgical techniques have been used for diaphragmatic repair such as synthetic materials and autologous grafts. Unfortunately, these non-absorbable biomaterial patches do not grow with the child and mechanically-mismatching with native tissue also causes many complications. Decellularized xenograft extracellular matrix (ECM) provides an alternative biomaterial in diaphragm tissue repair. In our study we used four male macaques (Macaca mulatta) after all ethical requirements. Native diaphragms were used for detergent-enzymatic decellularization for biological scaffolds obtainment. The fresh diaphragms were decellularized by modified agitation detergent-enzymatic method: 4% sodium deoxycholate and bovine pancreatic DNase for two days. Obtained decellularized diaphragm matrix was preserved important biological (removal of cell important cellular components without significantly altering the matrix structure) and biomechanical (axial strength) components. The loss of cells was confirmed by DNA quantification (approximately 60% of the nuclei material was removed from the diaphragm by the decellularization process). Immunohistochemical study demonstrated safety proteins of the ECM. Additional investigations are needed to prove the statement that decellularized non-human primate diaphragm scaffolds provides an alternative source for diaphragmatic tissue reconstruction, which will provide relevant preclinical data regarding for a potential clinical transfer.

Speaker
Biography:

Elena V Kuevda has completed her MD and PhD from Kuban State Medical University in Russia. She works as a Researcher in the Laboratory of Fundamental Research in the field of Regenerative Medicine at the Kuban State Medical University in Russia. She has published more than 40 papers in reputed journals both in Russia and abroad.

Abstract:

Bone regeneration is a multi-round and complex process combining scaffold creation and cell source selection. Several polymeric sponge and gel synthetic materials with different pore sizes seeded with rat bone marrow-derived stem cells (MSCs) and adipose stem cells (ASCs) were used as bone biodegradable grafts. Mineral substance powder of rat longitudinal bones was used as a control, MSCs and ASCs seeded on the plastic flasks were used as a positive control for cells attachment and growth. Grafts biocompatibility was tested with XTT test after 48 hours incubation under standard conditions. Cell viability and scaffold cytotoxicity indices were calculated in percentage. Almost all gel-based scaffolds demonstrated affinity to ASCs, cell viability indices varied from 6.72% to 78.17%, cytotoxicity indices spread from 6.13% to 37.57%. For MSCs seeded gel grafts cell viability was completely the same and varied from 5.87% to 47.75%, cytotoxicity of the scaffolds was from 4.25% to 32.45%. All sponge-based grafts showed high biocompatibility and ASCs affinity with cell viability about 67.88% and cytotoxicity about 29.16%. MSCs viability on the sponge scaffolds was about 54.27%, cytotoxicity was 15.94%. The control cell viability data for bone mineral powder was 70.76% for ASCs and 19.49% for MSCs; cytotoxicity for ASCs was 30.17% and 18.84% for MSCs. Thus, both stem cell lines preferable attached to sponge grafts which maintained the 3D structure of the bone with the adhesion not only on the top of the scaffold but inside. ASCs seemed to be less particular about the 3D organization of the material so MSCs are preferable to use at the initial step of graft evaluation to choose the best stereochemical bone mock polymer. Sponge-based scaffolds have enough capabilities to become promising source for tissue-engineered bone construction after additional investigation.

Speaker
Biography:

Elena V Kuevda has completed her MD and PhD from Kuban State Medical University in Russia. She works as a Researcher in the Laboratory of Fundamental Research in the field of Regenerative Medicine at Kuban State Medical University in Russia. She has published more than 40 papers in reputed journals both in Russia and abroad.

Abstract:

We evaluated adipose stem cells (ASCs) and bone marrow-derived stem cells (MSCs) for acellular esophagus and diaphragm scaffolds recellularization. ASCs and MSCs were isolated from male Wistar rats according to published protocols. Cells were cultivated in DMEM until the third passage with cell proliferative activity calculation. Both ASCs and MSCs were subjected to induced differentiation for verification of stem cells implementation. After 80% confluence achievement cells were detached, centrifuged, resuspended in DMEM and seeded on top of the scaffolds at the density 3×105 per well. Acellular esophagus and diaphragm matrices were obtained after detergent-enzymatic decellularization with 4% sodium deoxycholate with EDTA and bovine pancreatic DNAse according to our previously described protocols. The quality of obtained scaffolds was proved with histological staining and residual DNA quantification. Both ASCs and MSCs demonstrated resembling differentiation in 3 cells lines: Adipocytes, chondrocytes and osteocytes. Cell proliferation activity for ASCs was significantly higher. Cell viability and cytotoxicity indices for acellular matrices were calculated with XTT assay and alamar blue staining after 48 of cultivation. Acellular esophagus matrix demonstrated similar cell viability for both ASCs and MSCs recellularization (35.64% and 32.945, respectively). Decellularized diaphragm showed less affinity to ASCs (0.69%) comparing to MSCs (25.09%). The phenomenon could be specified after further studies of adhesive and proliferative properties of ASCs and affinity to the skeletal muscles. Adjustment of cell suspension introduction method from on top to perfusion seems reasonable for diaphragm scaffold for better cell attachment and penetration. ASCs are promising sources for smooth muscle matrices recellularization. The choice of cell line should be defined by cell suspension introduction method and cytotoxic properties of the scaffold itself. 

Jin Hyun Kim

Gyeongsang National University Hospital, South Korea

Title: Paricalcitol protects the kidney injury against radiocontrast in mice
Speaker
Biography:

Jin Hyun Kim is from the Gyeongsang National University Hospital, South Korea.

Abstract:

Radiocontrast-induced nephropathy (RCIN) is an important problem in clinical settings. However, strategies to prevent RCIN have been suboptimal. Paricalcitol was recently found to be effective in a variety of renal animal models, so it was hypothesized that paricalcitol would prevent RCIN. RCIN was induced in rats by injection of the radiocontrast medium Ioversol in addition to inhibition of prostaglandin and nitric oxide synthesis. Administration of two doses of paricalcitol before the induction of nephropathy significantly reduced the renal dysfunction and histologic tubular injury. The apoptosis of renal tubular cells was inhibited by paricalcitol. Oxidative stress markers such as 8-OhdG and NOX-2, NADPH oxidase, were highly expressed in nephropathy rat model, but attenuated by paricalcitol administration. β-galactosidase, one of markers of cellular senescence, increased in tubules after contrast infusion. This was alleviated by paricalcitol. Furthermore, the expression of LC3, PINK1 and Parkin, representatives of mitochondrial autophagy, after radiocontrast injection was highly attenuated by administration of paricalcitol, suggesting that the effects of paricalcitol might be mediated by the autophagy pathway. These findings suggest that paricalcitol may have potential as a new therapeutic approach to prevent RCIN.

Speaker
Biography:

Elahe Bahremandi Toloue has received her BS degree in Physics from the University of Isfahan in 2007 and MS degree in Solid State Physics from the Islamic Azad University of Tehran in 2012. She is currently a Medical Engineering student pursuing second Master’s degree at the Isfahan University of Medical Sciences.

Abstract:

Statement of the Problem: Already poly 3-hydroxybutyrate (PHB)-chitosan electrospun scaffold has been studied in tissue engineering applications. To enhance the mechanical properties of polymer based scaffolds, adding ceramic component to them has mostly been a proper solution. Alumina is one of the most biocompatible ceramics with good corrosion resistance and wear resistance. Studies show that, among various structures of ceramics, the fibrous structures are better than other structures for increasing the mechanical properties due to the possibility of aligning with the fibrous spun. In this research, the effects of alumina nanowires on the structural and mechanical properties of poly-3-hydroxybutyrate-chitosan electrospun scaffolds were evaluated.

Materials & Methods: Initially, 20 wt% of chitosan was added to a 0.09% wt. P3HB dissolved in trifluoroacetic acid solution. Al2O3 nanowires at different weight percentages (5% and 10%) were added to P3HB-chitosan polymer solutions and then spun.

Findings: Scanning electron microscopy (SEM) showed the average diameter of the fibers increased by increasing of Al2O3 nanowires from 336 to 494 nm. In addition, evaluation of porosity with the use of the MATLAB software program and SEM photomicrographs have been shown with increasing Al2O3 nanowires, porosity decreases from 82 to 81%. FTIR evaluations also showed the distribution of alumina nanowires in the composite scaffolds. The result of mechanical properties showed that tensile strength were 1.33 MPa and 1.07 MPa for the scaffolds containing 5 and 10% wt. alumina nanowires respectively, while 0.33 MPa has been measured for PHB-chitosan scaffold without alumina nanowires. It can be concluded that the addition of alumina ceramic nanowire has increased the mechanical properties of the polymeric scaffold, although adding of higher alumina percentages due to agglomeration has less effect on mechanical properties improvement.

Conclusion: Therefore, using Al2O3 nanowire in P3HB-chitosan electrospun scaffolds is a key to increase the mechanical properties of the mentioned scaffolds without undesirable effect on structural properties.

Speaker
Biography:

Elahe Bahremandi Toloue has received her BS degree in Physics from the University of Isfahan in 2007 and MS degree in Solid State Physics from the Islamic Azad University of Tehran in 2012. She is currently a Medical Engineering student pursuing second Master’s degree at the Isfahan University of Medical Sciences.

Abstract:

Background & Aim: Tissue engineering vascular graft (TEVG) is an advanced method for cardiovascular disease treatment. A major obstacle to the development of TEVG is the biomimetic scaffold component. Scaffold requirements include matching the mechanical, biological and structural properties with those of native vessels. Aim of this work is to fabricate and characterization of bi-layered, biodegradable and biomimmetic scaffold based on poly-(glycerol sebacate) PGS and poly-(ε-caprolactone) PCL.

Materials & Methods: Electrospun bi-layer scaffold was composed of inner layer; fabricated from PGS:PCL (2:1) and outer layer made from PCL since the inner/outer thickness was 2:1. Structural and mechanical properties of the scaffold were assessed and compared to the blood vessels. Hemocompatibility was evaluated using normal human whole blood according to the ISO 10993‑4.

Results: The scanning electron microscope (SEM) results showed that the fibers have a uniform diameter less than 1 µ and surface porosity of the structure is more 85% and it was interconnected. Mechanical evaluation of the bi-layer scaffold showed that its elastic modulus (12.8±1.4 MPa), elongation (210±21.7%) and ultimate strength (1.6±0.4 MPa) were comparable with those of native vessels. Hemocompatibility tests according to hemolysis, platelet adhesion and blood coagulation time revealed that the scaffold was highly hemocompatible that it would be related to biomimetic structure in addition to chemical composition.

Conclusion: This study suggests that the bi-layered PGS:PCL (2:1)/PCL fibrous scaffolds mimicked the structure and mechanical properties of native vine tissues and would potentially be suitable for the TEVG. Morphology of fibers has a significant effect on blood compatibility and mechanical properties in electrospun scaffold and may lead to proper biological response.

  • Regenerative Medicine | Stem Cell Therapy | Tissue Engineering
Location: Seletar
Speaker

Chair

Claire Henchcliffe

Weill Cornell Medical Center, USA

Speaker

Co-Chair

Nadia Benkirane-Jessel

Inserm - French National Institute of Health and Medical Research, France

Session Introduction

Tatyana Zharikova

I.M. Sechenov First Moscow State Medical University, Russia

Title: Russia’s landscape in regenerative medicine

Time : 11:20-11:40

Speaker
Biography:

Tatyana Zharikova did her Residency at the Department of Surgery from 2010-2011, second Residency (2011-2013) and PhD (2016) at the Department of Urology of the I.M. Sechenov First Moscow State Medical University. She is a Research Fellow of the Research Institute for Uronephrology and Reproductive Health. She is also a Research Fellow of the Institute for Regenerative Medicine (IRM) and became Deputy Director of the Institute for Regenerative Medicine (IRM) in 2017.

Abstract:

The main goal of regenerative medicine (RM) is to restore damaged organs and tissues using molecular, cell and tissue engineering approaches. In this aspect, RM can be presented as a part of the new world health care paradigm (translational and personalized medicine), which dedicates to optimize healthcare system using novel products all around the world. Being a member of the international community, the Russian Federation (RF) is involved in this process. The aim of this presentation is to critically evaluate the regenerative medicine state in the Russian Federation in the movement of the global changes. In the RF, private investors, government and the Russian Academy of Science have a particular interest in RM. From 2010, first-rate public funds, who support fundamental (RFBR) and fundamental-applied researches (RSF), regularly finance cutting-edge scientific projects in this field. To date, there is an annual double increase in quantity of publications related to RM in the RF. The main RM areas in Russia concern the application of mesenchymal and induced stem cells in bone tissue and vessel regeneration. There are number of research groups, who investigate neural tissue, liver and pancreas regeneration. Regenerative and reconstructive urology requires a special attention because first operations on urethra restoration using tissue engineered constructs were carried out on humans. To create a legal framework in the field of RM, the government passed the law on cell products in 2017. Thus, RM is intensively developing in Russia now. However, unbiased problems (insufficient financial support, low level of international collaborations, low publication activity and innovation passivity) still exist. The solution of them will determine the further development of this promising field in Russia.

Peter Timashev

I.M. Sechenov First Moscow State Medical University, Russia

Title: Laser structuring technologies for tissue engineering

Time : 11:40-12:00

Speaker
Biography:

Peter Timashev has worked on the development of novel biodegradable polymers and hybrid and ceramic biocompatible materials for laser additive technologies. His studies, which discuss the 2PP formation of 3D scaffolds inducing the osteogenic differentiation of stem cells, their mechanical and surface features and in vivo fluorescent imaging of their degradation rates, underlie the development of laser-induced structure formation for bone tissue engineering.

Abstract:

Statement of the Problem: To date, numerous achievements in personalized medicine, i.e. medicine based on an individual approach to each clinical case, have significantly increased possibilities in reconstructive and replacement surgery. Personalization of treatment is crucial to rise the efficacy of tissue restoration and to reduce the risk of side effects. One of the strategies in reconstructive therapy is based on tissue engineering methods, which allow the restoration of tissue integrity and functions and use porous biodegradable matrices. These matrices become a substrate for progenitor cell adhesion and stimulate reparative processes within recipient’s tissues.

Methodology & Theoretical Orientation: Success in the development of cell-laden matrices was achieved in bone tissue regeneration when high-strength and chemically stable 3D matrices were fabricated via two-photon polymerization (2PP) and applied. This technique allows the use of a large material variety for scaffold fabrication with the possibility of controlling accurately their microarchitecture and surface roughness to increase matrix functionality. Moreover, the use of 2PP in combination with other microfabrication methods can significantly increase the reproduction rate of tailor-made scaffolds and make the application of even more different materials possible. The 2PP structure functionalization permits us to deposit and to control the release of biologically active compounds and drugs.

Conclusion & Significance: Thus, the 2PP technique enables the personalized fabrication of tailor-made cell-laden matrices, which reproduce native tissue architectonics, and the translation of its use into clinical practice.

Speaker
Biography:

Ilgar S Mamedov has completed his PhD in Dermatology and Biophysics at the Russian State Medical University, Russia. He continued his professional education in Clinical Laboratory Diagnostics at Russian State Medical University during 2003. He was an Associate Professor at the Russian State Medical University and was the Head of Clinical Diagnostic Laboratory at the Moscow Clinical Diagnostic Center. Currently he is the Director of the Chromsystemslab, Russia.

Abstract:

A mass spectrometer detects the mass of ionized molecules. Many of these molecules are compounds found in biological fluids and are integral intermediates of clinical biochemistry. Metabolites are the substrates and products of the chemical reactions that constitute life. As such, they comprise an enormously heterogeneous mixture of compounds and compound classes (e.g., sugars, amino acids, lipids, organic acids and biogenic amines). This alone leads to significant issues with the provision of metabolomics, as technological methods ideal for the characterization of amino acids are likely to be not enough for the characterization of steroids. Despite this, most metabolomics platforms now detect hundreds to thousands of compounds, covering the majority key biochemical pathways. Good design of experiments is absolutely needs to a successful metabolomics analysis sample. For example, clinical samples are likely to be extremely variable and often even small changes in metabolite concentration are of interest and thus hundreds to thousands of samples per state may be required for sufficient statistical power. In contrast, well-defined cell culture experiments (for example, where cells are exposed to drug treatments) may be characterized by low variability and the effects may be large, so a handful of replicates may be sufficient. Whether one is performing a targeted or untargeted metabolomics analysis, the process of data analysis for MS is relatively unchanged. Statistical analysis is performed and the dataset is put about, regarding biochemical pathways, or in clinical studies, stratified with respect to clinical outcomes and patient data. When performing any analysis, it is critical to have a good understanding of the raw data, the statistics to be applied, the fundamentals of biochemistry and the biological question to be addressed. Generally, metabolomics can provide the greatly useful information in the medical field, the discovery of disease biomarkers, the finding of novel therapeutic agents and the examination of pathogenesis mechanisms behind various diseases. The present report describes a new method of diagnostics of illnesses of an exchange purines and pyrimidines with the use of HPLC the data is presented to combinations with electro spray mass spectrometry. Procedure of the analysis from pre-analytical stage to interpretation of the data of a liquid chromatography-mass spectrometry, quality assurance of the data of the analysis, mass spectrometer parameters and chromatographic research conditions of purines, pyrimidines and the metabolites is in detail described by the given technique.

Speaker
Biography:

Vladimir Mironov has graduated from The Ivanovo State Medical University (MD) in Ivanovo, Russia and obtained his PhD in Developmental Biology at The Second Moscow Medical University in Moscow, Russia. He has worked at Max Plack Institute for Psychiatry, Germany and then at the Department of Regenerative Medicine and Cell Biology of The Medical University of South Carolina, USA, where he was the Director of Advanced Tissue Biofabrication Research Center. He has worked several years in Brazil as FAPESP and CNPq funded Visiting Professor at The Division of 3D Technology at The Renato Archer Center for Information Technology in Campinas, Brazil and at The Life Science Division of The National Metrology Center (InMetro) in Rio de Janeiro, Brazil. He has also worked as a Chief Scientific Officer of Russian start-up 3D Bioprinting Solutions which developed first Russian multifunctional 3D Bioprinter Fabion and print a first functional animal organ; mouse thyroid gland.

Abstract:

Tissue spheroids have been proposed to use as building blocks in biofabrication and 3D bioprinting technologies. Label-based magnetic forces-driven 2D patterning of tissue spheroids requires cell labeling by magnetic nanoparticles. Recently novel label-free approach for magnetic levitational assembly has been introduced. Here we report a first time rapid assembly of 3D tissue engineered construct using scaffold-free and label-free magnetic levitation of tissue spheroids. Tissue spheroids (so-called chondrospheres) of standard size and shape capable of tissue fusion have been biofabricated using non-adhesive cell culture flasks from primary culture of ovine chondrocytes. Label-free magnetic levitation has been performed using experimental set with permanent magnets in presence of gadolinium in cell culture media which enables magnetic levitation. Potential toxic effect of gadolinium has been systematically evaluated. Mathematical modeling and computer simulations have been used for modeling of magnetic field and kinetics of tissue spheroids assembly into 3D tissue constructs. Plastic beads have been initially used as physical analogs of tissue spheroids for determining an optimal regime of magnetic levitation in presence of parmagnetic gadolinium medium. It has been shown that chondrospheres were able to rapidly assemble into 3D tissue construct in the permanent magnetic field in presence of gadolinium in cell culture media. Thus, label-free magnetic levitation of tissue spheroids represents a perspective approach for rapid scaffold-free 3D biofabrication and an attractive alternative to label-based magnetic tissue engineering.

Denis Butnaru

I.M. Sechenov First Moscow State Medical University, Russia

Title: Tissue engineered urethral substitution: Recent trends and our results

Time : 12:40-13:00

Speaker
Biography:

Butnaru Denis did his Residentship and PhD at the Department of Urology of the I.M. Sechenov Moscow State Medical Academy in 2004 and 2008, respectively. Since 2010, he has been actively working on the issues of reconstructive urogenital surgery. He has worked as the Head of the Surgical Department at the Urological Clinic from 2011-2012 and in 2012, he became the Head of the Department of Reconstructive-Plastic Uronephrology at the Uronephrology Research Institute of the I.M. Sechenov First Moscow State Medical University. He has worked as an Associate Professor of the Department of Urology at the I.M. Sechenov First Moscow State Medical University in 2015 and was then appointed as the Deputy Director of Research of the Uronephrology Research Institute. Since 2016, he has been working as the Director of the Institute for Regenerative Medicine (IRM).

Abstract:

Strictures and abnormalities of the urethra are still considered as complex urological problems. In such patients, the most effective treatment option is urethroplasty (anastomotic or substitution). Substitution urethroplasty implies widening the urethral lumen using flaps or grafts (e.g., buccal mucosa, foreskin, retroauricular or penile skin). Unfortunately, conventional approaches are less effective in case of longer and/or recurrent strictures. This requires development of novel treatment techniques such as implantation of the tissue-engineered urethra. However, one of the major challenges in growing any tissue-engineered organ is finding a proper material for its scaffold. This report reviews recent advances and perspectives in tissue-engineered urethral reconstruction and is particularly focused on using both acellular and recellularized constructs in humans and animal models.

Sergey Suchkov

I.M. Sechenov First Moscow State Medical University, Russia

Title: Antibodies with functionality as unique biomarkers and targets in drug discovery and regenerative medicine

Time : 14:00-14:20

Speaker
Biography:

Sergey Suchkov has completed his graduation from Astrakhan State Medical University and awarded with MD, PhD at the I.M. Sechenov Moscow Medical Academy and Doctorship degree at the National Institute of Immunology, Russia. He was a Senior Researcher, Koltzov Institute of Developmental Biology and was the Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. Currently he is a Chair, Department for Personalized and Translational Medicine, I.M. Sechenov First Moscow State Medical University. He is a Member of the New York Academy of Sciences, USA; American Chemical Society (ACS), USA; American Heart Association (AHA), USA; EPMA (European Association for Predictive, Preventive and Personalized Medicine), Brussels, EU; ARVO (American Association for Research in Vision and Ophthalmology); ISER (International Society for Eye Research); and PMC (Personalized Medicine Coalition), USA.

Abstract:

Catalytic Abs (catAbs) are multivalent immunoglobulins (Igs), endowed with a capacity to hydrolyze the antigenic substrate. In this sense, proteolytic Abs (or Ab-proteases) represents Abs endowed with a capacity to provide proteolytic effects. Ab-proteases were shown to occur at clinical courses and evidently correlate with the severity of the disease. A situation of much greater interest is occurred in multiple sclerosis (MS) which would demonstrate some new potential molecular targets to be selected for constructing newer diagnostic tools and setting up newer drug design as well. Anti-MBP autoAbs from MS patients exhibited sequence-specific proteolytic cleavage of MBP. The activity of Ab-proteases markedly differs: (1) Between MS patients and healthy controls, (2) Among MS patients with different types of the course to be the highest and thus dominate in a progradient course, progression phase, in particular. The activity of the Ab-proteases revealed significant correlation with scales of demyelination and thus with the disability of the patients as well. Moreover, when bursts of the Ab-associated proteolytic activity are evident, the pre-early stages of the exacerbation could be predicted, even at no seeing any clinical manifestations. And when we saw a stable growth of the activity, we could predict changing of a remitting type (moderate one) into the pro-gradient type (severe one) prior to changing of the clinical manifestations. Ab-mediated proteolysis of MBP results in generating a set of peptides. The final statistical data revealed six sites of preferential proteolysis. Most of those sites are located within the immunodominant regions of MBP. In contrast to canonical proteases, for Ab-proteases, there is an extra set of cleavage sites in the targeted autoantigens focused predominantly at the immunodominant sites of MBP. The activity of Ab-proteases was first registered at the subclinical stages 1-2 years prior to the clinical illness. About 24% of the direct MS-related relatives were seropositive for low-active Ab-proteases from which 38% of the seropositive relatives established were being demonstrating a stable growth of the activity for 2 years under the study. Moreover, low-active Ab-proteases in at-risk persons (at the subclinical stages) and primary clinical and MRT manifestations observed were coincided with the activity to have its mid-level reached. And registration in the evolution of highly immunogenic Ab-proteases to attack other sites predominantly would illustrate either risks of transformation of subclinical stages into clinical ones or risks of exacerbations to develop. Of tremendous value is Ab-proteases directly affecting remodeling of tissues with multilevel architectonics, for instance, myelin and by changing sequence specificity of the Ab-mediated proteolysis one may reach reduction of a density of points of the negative proteolytic effects within the myelin sheath and minimizing scales of demyelination. Moreover, Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of principally new catalysts with no natural counterparts. So, further studies on Ab-mediated MBP degradation and other targeted Ab-mediated proteolysis may provide a supplementary (diagnostic, preventive and therapeutic) tool for assessing the disease progression, predicting disability of the patients and preventing the progression.

Vladimir Sukhorukov

I.M. Sechenov First Moscow State Medical University, Russia

Title: Regenerative medicine and its armamentarium in promoting personalized pediatric healthcare

Time : 14:20-14:40

Speaker
Biography:

Vladimir Sukhorukov is the Head of the General Pathology Department at N.I. Pirogov Russian National Research Medical University and Professor of the Center for Personalized Medicine in I.M. Sechenov First Moscow State Medical University, Russia. Currently he is associated with an organization of investigations in different aspects of pediatric pathology (mitochondrial diseases, other inherited metabolic diseases, neuromuscular diseases, etc.) with use of chromatography, mass-spectroscopy, molecular-genetic, immunohistochemical studies and other.

Abstract:

The development of regenerative medicine is one of the most effective trends in personalized healthcare of the future to come. In turn, one of the most important fields of the activities is Personalized Pediatric Healthcare Services (PPHCS) to be developed as key predictive, diagnostic, preventive, therapeutic and rehabilitative tools to ensure healthy and wealthy life. The development of the pediatric aspects of regenerative medicine would include a number of features drastically distinguishing this segment of PM from the other ones: (1) Chronic disease often starts up as being asymptomatic in the early childhood. Accordingly, in this period namely, which would initiate with the marked efficiency preventive and prophylactic interventions, including those related to the direct applications of tools to be rooted from the regenerative medicine, (2) Childhood is a period to be opened for developing and flowering of most (including orphan and hereditary) of the diseases, because of their severity canonical healthcare services would not combat the latter. And it would thus be an area to suit the goals of regenerative medicine-related measurements. Potential progress in this direction can significantly reduce mortality and improve quality of life among those patients. It should be noted that those gains, particularly in the treatment of monogenic diseases, as occurring commonly in children, can be models for the development of new methods to illustrate regenerative potential of treatment as applicable to a scope of disorders mentioned, (3) An important feature of the trend and thus the tools is the high-level regenerative and plasticity-related potential of children's tissues. This capacity greatly strengthens regenerative efficacy, both in terms of tissue and intracellular regeneration. As an example of the later, we will present our data on the compensatory origin of mitochondria proliferation, counterweighing clinical manifestations of some of the hereditary diseases.

Alain Chapel

IRSN- Institute of Radioprotection and Nuclear Safety, France

Title: Stem cell therapy for the treatment of severe tissue damage after radiation exposure
Speaker
Biography:

Alain Chapel is a Scientific Investigator at IRSN, Laboratory of Radiopathology and Experimental Therapies. For 20 years, he has been developing gene and cell therapy using non-human primates and immune-tolerant mice and rats to protect against the side effects of radiation. He has developed representative experimental models of SAI to investigate the effect of radiation on both radiosensitive hematopoietic cells and their bone marrow microenvironment. In collaboration with Saint-Antoine Hospital (Paris, France), he has contributed to the first reported correction of deficient hematopoiesis in patients (graft failure and aplastic anemia) thanks to intravenous injection of MSCs restoring the bone marrow microenvironment, mandatory to sustain hematopoiesis after total body irradiation. Currently his work focuses on the development of radio-induced bone marrow aplasia using human hematopoietic stem cells derived from human IPS. He is a Member of various learned national and international societies: European Bone Marrow Transplantation Group (EBMT), American Society for Hematology, International Society of Stem Cell Research, Société Francaise de Greffe moelle et de thérapie cellulaire. He is an Associate Editor of five international journals: World Journal of Stem CellsWorld Journal of Gastrointestinal SurgeryWorld Journal of RadiologyThe Open Gene Therapy Journal and Journal of Clinical Rehabilitative Tissue Engineering Research

Abstract:

The late adverse effects of pelvic radiotherapy concern 5 to 10% of them, which could be life threatening. However, a clear medical consensus concerning the clinical management of such healthy tissue sequela does not exist. Our group has demonstrated in preclinical animal models that systemic MSC injection is a promising approach for the medical management of gastrointestinal disorder after irradiation. We have shown that MSC migrate to damaged tissues and restore gut functions after irradiation. The clinical status of four first patients suffering from severe pelvic side effects resulting from an over-dosage was improved following MSC injection in a compassionate situation. A quantity of 2×106-6×106 MSC/kg was infused intravenously to the patients. Pain, hemorrhage, frequency of diarrheas and fistulisation as well as the lymphocyte subsets in peripheral blood were evaluated before MSC therapy and during the follow-up. Two patients revealed a substantiated clinical response for pain and hemorrhage after MSC therapy. In one patient pain reappeared after 6 months and again substantially responded on a second MSC infusion. At the beginning, fistulisation process could be stopped in one patient resulting in a stable remission for more than 3 years of follow-up. The frequency of painful diarrhea diminished from an average of 6/d to 3/d after the 1st and 2/d after the 2nd MSC injection in one patient. In all patients, prostate cancer remained in stable complete remission. A modulation of the lymphocyte subsets towards a regulatory pattern and diminution of activated T cells accompanies the clinical response in refractory irradiation-induced colitis. No toxicity occurred. MSC therapy was safe and effective on pain, diarrhea, hemorrhage, inflammation, fibrosis and limited fistulisation. For patients with refractory chronic inflammatory and fistulising bowel diseases, systemic MSC injections represent a safe option for salvage therapy.

  • Special Session
Location: Seletar

Session Introduction

Alain Chapel

IRSN- Institute of Radioprotection and Nuclear Safety, France

Title: Stem cell therapy for the treatment of severe tissue damage after radiation exposure

Time : 15:00-15:45

Speaker
Biography:

Alain Chapel is a Scientific Investigator at IRSN, Laboratory of Radiopathology and Experimental Therapies. For 20 years, he has been developing gene and cell therapy using non-human primates and immune-tolerant mice and rats to protect against the side effects of radiation. He has developed representative experimental models of SAI to investigate the effect of radiation on both radiosensitive hematopoietic cells and their bone marrow microenvironment. In collaboration with Saint-Antoine Hospital (Paris, France), he has contributed to the first reported correction of deficient hematopoiesis in patients (graft failure and aplastic anemia) thanks to intravenous injection of MSCs restoring the bone marrow microenvironment, mandatory to sustain hematopoiesis after total body irradiation. Currently his work focuses on the development of radio-induced bone marrow aplasia using human hematopoietic stem cells derived from human IPS. He is a Member of various learned national and international societies: European Bone Marrow Transplantation Group (EBMT), American Society for Hematology, International Society of Stem Cell Research, Société Francaise de Greffe moelle et de thérapie cellulaire. He is an Associate Editor of five international journals: World Journal of Stem CellsWorld Journal of Gastrointestinal SurgeryWorld Journal of RadiologyThe Open Gene Therapy Journal and Journal of Clinical Rehabilitative Tissue Engineering Research

Abstract:

The late adverse effects of pelvic radiotherapy concern 5 to 10% of them, which could be life threatening. However, a clear medical consensus concerning the clinical management of such healthy tissue sequela does not exist. Our group has demonstrated in preclinical animal models that systemic MSC injection is a promising approach for the medical management of gastrointestinal disorder after irradiation. We have shown that MSC migrate to damaged tissues and restore gut functions after irradiation. The clinical status of four first patients suffering from severe pelvic side effects resulting from an over-dosage was improved following MSC injection in a compassionate situation. A quantity of 2×106-6×106 MSC/kg was infused intravenously to the patients. Pain, hemorrhage, frequency of diarrheas and fistulisation as well as the lymphocyte subsets in peripheral blood were evaluated before MSC therapy and during the follow-up. Two patients revealed a substantiated clinical response for pain and hemorrhage after MSC therapy. In one patient pain reappeared after 6 months and again substantially responded on a second MSC infusion. At the beginning, fistulisation process could be stopped in one patient resulting in a stable remission for more than 3 years of follow-up. The frequency of painful diarrhea diminished from an average of 6/d to 3/d after the 1st and 2/d after the 2nd MSC injection in one patient. In all patients, prostate cancer remained in stable complete remission. A modulation of the lymphocyte subsets towards a regulatory pattern and diminution of activated T cells accompanies the clinical response in refractory irradiation-induced colitis. No toxicity occurred. MSC therapy was safe and effective on pain, diarrhea, hemorrhage, inflammation, fibrosis and limited fistulisation. For patients with refractory chronic inflammatory and fistulising bowel diseases, systemic MSC injections represent a safe option for salvage therapy.

  • Tissue Regeneration | Bone Transplantation | Tumor Cell Science
Location: Seletar

Session Introduction

Siti Sarah Daud

National University of Singapore, Singapore

Title: Integrative approaches through transcriptome profiling to identify subset-specific gene activity in myeloma

Time : 15:45-16:05

Speaker
Biography:

Siti Sarah Daud has received her PhD in Leukemia Research from School of Medicine, Cardiff University, UK in 2014. Prior to that, she pursued Masters in Medical Science, focusing on childhood leukemia at University of Malaya, Malaysia. During her postgraduate years, she had served at Pediatric Oncology Research Unit and was involved in chimerism typing for post-hematopoietic stem cell transplant patients at University of Malaya. Presently, she holds a Research Fellow Position at Department of Pediatrics, National University of Singapore. Her current research focuses on understanding the relation of heterogeneity in multiple myeloma subpopulations towards natural killer-cell immune response. She also has experience to ascertain low-input transcriptome workflows for human and non-human primate’s platforms.

Abstract:

Statement of the Problem: The heterogeneous subsets in hematological malignancy such as multiple myeloma may be better characterize when tumor profiling were performed in multiple different dimensions. An integrative approach is needed to predict cell subset with potentially higher clonogenic potential and this has been a long-standing question in myeloma. However when analyzing bone marrow (BM) aspirates for RNA studies, one major challenge is to properly exclude signatures of non-myelomatous populations from the actual signatures of myeloma subsets that coexist within the same BM niche. Although CD138 is constitutively expressed in aberrant plasma cells, several patients do not express CD138 at high levels. These cases warrant further investigation before they can be subjected for downstream gene expression studies. Additional markers such as CD319 or CD229 were found to be useful since they were highly expressed in myeloma but not in normal plasma cells.

Methodology & Theoretical Orientation: The tumor cells identified from primary CD138hi myeloma population were sorted into four subsets using fluorescence-activated cell sorting based on expression of CD19, CD20, CD27 and CD56 surface markers. The sorted cells were subjected to RNA-sequencing and low-input microarray workflows.

Findings: The overall proximity between myeloma subsets were assessed using eigengene modules and cluster analyses. For myeloma that lack CD19 surface marker density, several distinct cellular immunophenotypes were identified. Two of the subsets show large similarity in transcription profile. Since they also lack CD27 surface expression, these clones could actually escape apoptosis induced by CD27-CD70 ligand interactions, as compared to the rare CD27hi myeloma cells.

Conclusion & Significance: Together, high-dimensional data extracted using combination of clinically relevant markers along with sufficient set of exclusion markers will permit mining for functional differences or similarity between subsets that might not be previously manifested in the bulk primary tumor population.

Lee Ha Yin

Duke–NUS Medical School, Singapore

Title: Targeting the unique properties of glucose in cancer through calcium-PP2A-RIPK1 pathway

Time : 16:05-16:25

Speaker
Biography:

Ha Yin Lee has her research focus on cancer metabolism and she has been investigating the potential therapeutic target in cancer metabolism. She has completed her graduation degree in 2015 from NUS.

Abstract:

Cancer cells have enhanced glycolysis in the presence of oxygen, a phenomenon known as the Warburg effect. Unlike normal cells, cancer cells are highly dependent on glucose for survival. Therefore, it was predicted that glycolysis inhibitors would selectively eliminate cancer cells. Contrary to prediction, commercially available glycolytic inhibitors have limited response on cancer cell inhibition. To fully understand how glucose deprivation kills cancer cells, we investigated the effects of glucose deprivation on different cancer cells. We showed that demethylation of the catalytic subunit of protein phosphatase 2A (PP2A) occurs uniquely in a subset of cancer cells that are sensitive to glucose deprivation. Glucose deprivation triggers an influx of calcium into the cytoplasm activating calcium/calmodulin-dependent protein kinase, CAMK1 and in turn, the PP2Ac demethylase PPME1. PP2Ac demethylation activates receptor-interacting serine/threonine protein kinase 1 RIPK1, which induces RIPK1-dependent cell death. PP2Ac demethylation and cell death are rescued with glucose and unexpectedly, with its non-metabolizable analog, 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor. These findings reveal that glucose could protect cells from cell death via the regulation of calcium signaling independent from its glycolytic properties and ATP levels. This is in sharp contrast to the current dogma of targeting the Warburg effect. We also found that after glucose removal, only a subset of cancer cells but not normal cells maintain critically low intracellular glucose levels. By targeting this unique property of glucose that is independent from glycolytic pathway, we can efficiently induce cancer cell death without affecting normal cells. Indeed, we successfully induced cell death on a subset of cancer cells but not normal cells by the combinational treatments of STF-31, a GLUT1 inhibitor that blocks the glucose transport and thapsigargin, which increases intracellular calcium concentration. Taken together, our results reveal a novel glucose sensing pathway that represents a potential therapeutic target in cancer.

Speaker
Biography:

Viantha Naidoo is currently a PhD student in Cell Biology in the Department of Human Biology at the University of Cape Town in South Africa. Her research interests lie in regenerative medicine and she is presently investigating pancreatic islet vascular and nerve regeneration after a 90% partial pancreatectomy in adult rats.

Abstract:

Background: The ability of pancreatic islets to maintain blood glucose homeostasis is compromised in diabetes, which has led to numerous past studies investigating islet regeneration. While promising, such investigations have not examined islet revascularization in models of regeneration, the importance of which has been clearly shown in islet transplantation. Furthermore, long-term islet function is thought to be linked to the longevity of its vasculature where pericytes, cells critical for angiogenesis and blood vessel stability, may play a pivotal role. However, investigations by others into islet regeneration are limited to one month after PPX.

Aim: The aim of this study was to investigate islet vascular growth at 30 and 90 days post 90% PPX, by examining islet capillary and pericyte density.

Methods: Fixed whole-mount tissue sections from 30 and 90 day post PPX and sham-operated adult male Wistar rat pancreata were multi-immunostained with anti-insulin, anti α smooth muscle actin and Lycopersicon esculentum lectin-FITC for islet, pericyte and vessel detection, respectively. Islets were imaged by confocal microscopy. 3D reconstructions of acquired Z-stacks were analyzed using Fiji software to determine islet size and vascular and pericyte density. Recorded fasting blood glucose values were included in the analysis.

Results: Thus far, our data show a trend of an increase in capillary and pericyte density and pericyte:capillary ratio (PPX>controls and PPX90D>PPX30D). No differences in islet distribution and blood glucose levels were observed among all groups.

Conclusion & Significance: The results indicate that islet vascular growth occurs until at least 90 days post PPX with no evidence of termination. This concurs with our previous investigation of islet cell proliferation, suggesting potential endurance of islet revascularization. The increase of the pericyte:capillary ratio suggests a stabilization of the vascular bed with an increase in mature vessels during the regenerative period, contributing to normal islet function.

Sahely Saha

National Institute of Technology, Rourkela, India

Title: Synthesis of TiO2 nanotubes over Ti6Al4V surface to improve osteocompatibility of bone implants

Time : 16:45-17:05

Speaker
Biography:

Sahely Saha is Research Scholar at the Department of Biotechnology and Medical Engineering, National Institute of Technology in India under the supervision of Dr. Amit Biswas. Her current area of research includes biomaterials and tissue engineering. Previously, she has completed her Master’s degree in Biotechnology and carried out a study based on bio-beneficiation of bauxite ore, as a part of her final year research work.

Abstract:

Statement of the Problem: Rapid growth has been witnessed in the field of implant fabrication, in the last decade. Titanium alloys are among the most used metallic biomaterials, particularly for orthopedic applications, as they have low specific weight, excellent mechanical properties, immense resistance to corrosion in biological fluids, good wear resistance and very low toxicity towards the host. Further, to improve bone fixation and enhance the biocompatibility of the titanium based implants, bone cements are used in conjugation with the implant materials during the joint replacement surgeries. However, such implants fail due to de-bonding of cementing material followed by accumulation of the particulate causing toxicity and cell death. Also, bone loosening might occur at the cement-prosthesis interface and/or cement-bone interface, thereby increasing the chances of implant failure by two-folds. To address this limitation, surface modification of Titanium implants has been considered to enhance the biocompatibility of the substrate.

Methodology & Theoretical Orientation: In the present study the surface of Ti6Al4V was modified through the synthesis of TiO2 nanotubes using anodic oxidation. The nanostructured surface was expected to enhance the surface area for cellular interaction and increase osteoconductive property of the implant without the release of toxic particles from coating material.

Findings: TiO2 nanotubes were synthesized and characterized for its morphology, surface roughness, wettability and osteo-compatibility.

Conclusion & Significance: It was observed from the study that the nanostructured surface significantly enhanced the osteoconductive property and biocompatibility of the Ti6Al4V implant surface.

  • Symposium

Session Introduction

Tatyana Zharikova

I.M. Sechenov First Moscow State Medical University, Russia

Title: Russia’s landscape in regenerative medicine
Speaker
Biography:

Tatyana Zharikova did her Residency at the Department of Surgery from 2010-2011, second Residency (2011-2013) and PhD (2016) at the Department of Urology of the I.M. Sechenov First Moscow State Medical University. She is a Research Fellow of the Research Institute for Uronephrology and Reproductive Health. She is also a Research Fellow of the Institute for Regenerative Medicine (IRM) and became Deputy Director of the Institute for Regenerative Medicine (IRM) in 2017.

Abstract:

The main goal of regenerative medicine (RM) is to restore damaged organs and tissues using molecular, cell and tissue engineering approaches. In this aspect, RM can be presented as a part of the new world health care paradigm (translational and personalized medicine), which dedicates to optimize healthcare system using novel products all around the world. Being a member of the international community, the Russian Federation (RF) is involved in this process. The aim of this presentation is to critically evaluate the regenerative medicine state in the Russian Federation in the movement of the global changes. In the RF, private investors, government and the Russian Academy of Science have a particular interest in RM. From 2010, first-rate public funds, who support fundamental (RFBR) and fundamental-applied researches (RSF), regularly finance cutting-edge scientific projects in this field. To date, there is an annual double increase in quantity of publications related to RM in the RF. The main RM areas in Russia concern the application of mesenchymal and induced stem cells in bone tissue and vessel regeneration. There are number of research groups, who investigate neural tissue, liver and pancreas regeneration. Regenerative and reconstructive urology requires a special attention because first operations on urethra restoration using tissue engineered constructs were carried out on humans. To create a legal framework in the field of RM, the government passed the law on cell products in 2017. Thus, RM is intensively developing in Russia now. However, unbiased problems (insufficient financial support, low level of international collaborations, low publication activity and innovation passivity) still exist. The solution of them will determine the further development of this promising field in Russia.

Peter Timashev

I.M. Sechenov First Moscow State Medical University, Russia

Title: Laser structuring technologies for tissue engineering
Speaker
Biography:

Peter Timashev has worked on the development of novel biodegradable polymers and hybrid and ceramic biocompatible materials for laser additive technologies. His studies, which discuss the 2PP formation of 3D scaffolds inducing the osteogenic differentiation of stem cells, their mechanical and surface features and in vivo fluorescent imaging of their degradation rates, underlie the development of laser-induced structure formation for bone tissue engineering.

Abstract:

Statement of the Problem: To date, numerous achievements in personalized medicine, i.e. medicine based on an individual approach to each clinical case, have significantly increased possibilities in reconstructive and replacement surgery. Personalization of treatment is crucial to rise the efficacy of tissue restoration and to reduce the risk of side effects. One of the strategies in reconstructive therapy is based on tissue engineering methods, which allow the restoration of tissue integrity and functions and use porous biodegradable matrices. These matrices become a substrate for progenitor cell adhesion and stimulate reparative processes within recipient’s tissues.

Methodology & Theoretical Orientation: Success in the development of cell-laden matrices was achieved in bone tissue regeneration when high-strength and chemically stable 3D matrices were fabricated via two-photon polymerization (2PP) and applied. This technique allows the use of a large material variety for scaffold fabrication with the possibility of controlling accurately their microarchitecture and surface roughness to increase matrix functionality. Moreover, the use of 2PP in combination with other microfabrication methods can significantly increase the reproduction rate of tailor-made scaffolds and make the application of even more different materials possible. The 2PP structure functionalization permits us to deposit and to control the release of biologically active compounds and drugs.

Conclusion & Significance: Thus, the 2PP technique enables the personalized fabrication of tailor-made cell-laden matrices, which reproduce native tissue architectonics, and the translation of its use into clinical practice.

Speaker
Biography:

Ilgar S Mamedov has completed his PhD in Dermatology and Biophysics at the Russian State Medical University, Russia. He continued his professional education in Clinical Laboratory Diagnostics at Russian State Medical University during 2003. He was an Associate Professor at the Russian State Medical University and was the Head of Clinical Diagnostic Laboratory at the Moscow Clinical Diagnostic Center. Currently he is the Director of the Chromsystemslab, Russia.

Abstract:

A mass spectrometer detects the mass of ionized molecules. Many of these molecules are compounds found in biological fluids and are integral intermediates of clinical biochemistry. Metabolites are the substrates and products of the chemical reactions that constitute life. As such, they comprise an enormously heterogeneous mixture of compounds and compound classes (e.g., sugars, amino acids, lipids, organic acids and biogenic amines). This alone leads to significant issues with the provision of metabolomics, as technological methods ideal for the characterization of amino acids are likely to be not enough for the characterization of steroids. Despite this, most metabolomics platforms now detect hundreds to thousands of compounds, covering the majority key biochemical pathways. Good design of experiments is absolutely needs to a successful metabolomics analysis sample. For example, clinical samples are likely to be extremely variable and often even small changes in metabolite concentration are of interest and thus hundreds to thousands of samples per state may be required for sufficient statistical power. In contrast, well-defined cell culture experiments (for example, where cells are exposed to drug treatments) may be characterized by low variability and the effects may be large, so a handful of replicates may be sufficient. Whether one is performing a targeted or untargeted metabolomics analysis, the process of data analysis for MS is relatively unchanged. Statistical analysis is performed and the dataset is put about, regarding biochemical pathways, or in clinical studies, stratified with respect to clinical outcomes and patient data. When performing any analysis, it is critical to have a good understanding of the raw data, the statistics to be applied, the fundamentals of biochemistry and the biological question to be addressed. Generally, metabolomics can provide the greatly useful information in the medical field, the discovery of disease biomarkers, the finding of novel therapeutic agents and the examination of pathogenesis mechanisms behind various diseases. The present report describes a new method of diagnostics of illnesses of an exchange purines and pyrimidines with the use of HPLC the data is presented to combinations with electro spray mass spectrometry. Procedure of the analysis from pre-analytical stage to interpretation of the data of a liquid chromatography-mass spectrometry, quality assurance of the data of the analysis, mass spectrometer parameters and chromatographic research conditions of purines, pyrimidines and the metabolites is in detail described by the given technique.

Speaker
Biography:

Vladimir Mironov has graduated from The Ivanovo State Medical University (MD) in Ivanovo, Russia and obtained his PhD in Developmental Biology at The Second Moscow Medical University in Moscow, Russia. He has worked at Max Plack Institute for Psychiatry, Germany and then at the Department of Regenerative Medicine and Cell Biology of The Medical University of South Carolina, USA, where he was the Director of Advanced Tissue Biofabrication Research Center. He has worked several years in Brazil as FAPESP and CNPq funded Visiting Professor at The Division of 3D Technology at The Renato Archer Center for Information Technology in Campinas, Brazil and at The Life Science Division of The National Metrology Center (InMetro) in Rio de Janeiro, Brazil. He has also worked as a Chief Scientific Officer of Russian start-up 3D Bioprinting Solutions which developed first Russian multifunctional 3D Bioprinter Fabion and print a first functional animal organ; mouse thyroid gland.

Abstract:

Tissue spheroids have been proposed to use as building blocks in biofabrication and 3D bioprinting technologies. Label-based magnetic forces-driven 2D patterning of tissue spheroids requires cell labeling by magnetic nanoparticles. Recently novel label-free approach for magnetic levitational assembly has been introduced. Here we report a first time rapid assembly of 3D tissue engineered construct using scaffold-free and label-free magnetic levitation of tissue spheroids. Tissue spheroids (so-called chondrospheres) of standard size and shape capable of tissue fusion have been biofabricated using non-adhesive cell culture flasks from primary culture of ovine chondrocytes. Label-free magnetic levitation has been performed using experimental set with permanent magnets in presence of gadolinium in cell culture media which enables magnetic levitation. Potential toxic effect of gadolinium has been systematically evaluated. Mathematical modeling and computer simulations have been used for modeling of magnetic field and kinetics of tissue spheroids assembly into 3D tissue constructs. Plastic beads have been initially used as physical analogs of tissue spheroids for determining an optimal regime of magnetic levitation in presence of parmagnetic gadolinium medium. It has been shown that chondrospheres were able to rapidly assemble into 3D tissue construct in the permanent magnetic field in presence of gadolinium in cell culture media. Thus, label-free magnetic levitation of tissue spheroids represents a perspective approach for rapid scaffold-free 3D biofabrication and an attractive alternative to label-based magnetic tissue engineering.

Denis Butnaru

I.M. Sechenov First Moscow State Medical University, Russia

Title: Tissue engineered urethral substitution: Recent trends and our results
Speaker
Biography:

Butnaru Denis did his Residentship and PhD at the Department of Urology of the I.M. Sechenov Moscow State Medical Academy in 2004 and 2008, respectively. Since 2010, he has been actively working on the issues of reconstructive urogenital surgery. He has worked as the Head of the Surgical Department at the Urological Clinic from 2011-2012 and in 2012, he became the Head of the Department of Reconstructive-Plastic Uronephrology at the Uronephrology Research Institute of the I.M. Sechenov First Moscow State Medical University. He has worked as an Associate Professor of the Department of Urology at the I.M. Sechenov First Moscow State Medical University in 2015 and was then appointed as the Deputy Director of Research of the Uronephrology Research Institute. Since 2016, he has been working as the Director of the Institute for Regenerative Medicine (IRM).

Abstract:

Strictures and abnormalities of the urethra are still considered as complex urological problems. In such patients, the most effective treatment option is urethroplasty (anastomotic or substitution). Substitution urethroplasty implies widening the urethral lumen using flaps or grafts (e.g., buccal mucosa, foreskin, retroauricular or penile skin). Unfortunately, conventional approaches are less effective in case of longer and/or recurrent strictures. This requires development of novel treatment techniques such as implantation of the tissue-engineered urethra. However, one of the major challenges in growing any tissue-engineered organ is finding a proper material for its scaffold. This report reviews recent advances and perspectives in tissue-engineered urethral reconstruction and is particularly focused on using both acellular and recellularized constructs in humans and animal models.

Speaker
Biography:

Sergey Suchkov has completed his graduation from Astrakhan State Medical University and awarded with MD, PhD at the I.M. Sechenov Moscow Medical Academy and Doctorship degree at the National Institute of Immunology, Russia. He was a Senior Researcher, Koltzov Institute of Developmental Biology and was the Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. Currently he is a Chair, Department for Personalized and Translational Medicine, I.M. Sechenov First Moscow State Medical University. He is a Member of the New York Academy of Sciences, USA; American Chemical Society (ACS), USA; American Heart Association (AHA), USA; EPMA (European Association for Predictive, Preventive and Personalized Medicine), Brussels, EU; ARVO (American Association for Research in Vision and Ophthalmology); ISER (International Society for Eye Research); and PMC (Personalized Medicine Coalition), USA.

Abstract:

Catalytic Abs (catAbs) are multivalent immunoglobulins (Igs), endowed with a capacity to hydrolyze the antigenic substrate. In this sense, proteolytic Abs (or Ab-proteases) represents Abs endowed with a capacity to provide proteolytic effects. Ab-proteases were shown to occur at clinical courses and evidently correlate with the severity of the disease. A situation of much greater interest is occurred in multiple sclerosis (MS) which would demonstrate some new potential molecular targets to be selected for constructing newer diagnostic tools and setting up newer drug design as well. Anti-MBP autoAbs from MS patients exhibited sequence-specific proteolytic cleavage of MBP. The activity of Ab-proteases markedly differs: (1) Between MS patients and healthy controls, (2) Among MS patients with different types of the course to be the highest and thus dominate in a progradient course, progression phase, in particular. The activity of the Ab-proteases revealed significant correlation with scales of demyelination and thus with the disability of the patients as well. Moreover, when bursts of the Ab-associated proteolytic activity are evident, the pre-early stages of the exacerbation could be predicted, even at no seeing any clinical manifestations. And when we saw a stable growth of the activity, we could predict changing of a remitting type (moderate one) into the pro-gradient type (severe one) prior to changing of the clinical manifestations. Ab-mediated proteolysis of MBP results in generating a set of peptides. The final statistical data revealed six sites of preferential proteolysis. Most of those sites are located within the immunodominant regions of MBP. In contrast to canonical proteases, for Ab-proteases, there is an extra set of cleavage sites in the targeted autoantigens focused predominantly at the immunodominant sites of MBP. The activity of Ab-proteases was first registered at the subclinical stages 1-2 years prior to the clinical illness. About 24% of the direct MS-related relatives were seropositive for low-active Ab-proteases from which 38% of the seropositive relatives established were being demonstrating a stable growth of the activity for 2 years under the study. Moreover, low-active Ab-proteases in at-risk persons (at the subclinical stages) and primary clinical and MRT manifestations observed were coincided with the activity to have its mid-level reached. And registration in the evolution of highly immunogenic Ab-proteases to attack other sites predominantly would illustrate either risks of transformation of subclinical stages into clinical ones or risks of exacerbations to develop. Of tremendous value is Ab-proteases directly affecting remodeling of tissues with multilevel architectonics, for instance, myelin and by changing sequence specificity of the Ab-mediated proteolysis one may reach reduction of a density of points of the negative proteolytic effects within the myelin sheath and minimizing scales of demyelination. Moreover, Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of principally new catalysts with no natural counterparts. So, further studies on Ab-mediated MBP degradation and other targeted Ab-mediated proteolysis may provide a supplementary (diagnostic, preventive and therapeutic) tool for assessing the disease progression, predicting disability of the patients and preventing the progression.

Speaker
Biography:

Vladimir Sukhorukov is the Head of the General Pathology Department at N.I. Pirogov Russian National Research Medical University and Professor of the Center for Personalized Medicine in I.M. Sechenov First Moscow State Medical University, Russia. Currently he is associated with an organization of investigations in different aspects of pediatric pathology (mitochondrial diseases, other inherited metabolic diseases, neuromuscular diseases, etc.) with use of chromatography, mass-spectroscopy, molecular-genetic, immunohistochemical studies and other.

Abstract:

The development of regenerative medicine is one of the most effective trends in personalized healthcare of the future to come. In turn, one of the most important fields of the activities is Personalized Pediatric Healthcare Services (PPHCS) to be developed as key predictive, diagnostic, preventive, therapeutic and rehabilitative tools to ensure healthy and wealthy life. The development of the pediatric aspects of regenerative medicine would include a number of features drastically distinguishing this segment of PM from the other ones: (1) Chronic disease often starts up as being asymptomatic in the early childhood. Accordingly, in this period namely, which would initiate with the marked efficiency preventive and prophylactic interventions, including those related to the direct applications of tools to be rooted from the regenerative medicine, (2) Childhood is a period to be opened for developing and flowering of most (including orphan and hereditary) of the diseases, because of their severity canonical healthcare services would not combat the latter. And it would thus be an area to suit the goals of regenerative medicine-related measurements. Potential progress in this direction can significantly reduce mortality and improve quality of life among those patients. It should be noted that those gains, particularly in the treatment of monogenic diseases, as occurring commonly in children, can be models for the development of new methods to illustrate regenerative potential of treatment as applicable to a scope of disorders mentioned, (3) An important feature of the trend and thus the tools is the high-level regenerative and plasticity-related potential of children's tissues. This capacity greatly strengthens regenerative efficacy, both in terms of tissue and intracellular regeneration. As an example of the later, we will present our data on the compensatory origin of mitochondria proliferation, counterweighing clinical manifestations of some of the hereditary diseases.

  • 1
Location: Seletar
Speaker

Chair

Claire Henchcliffe

Weill Cornell Medical Center, USA

Speaker

Co-Chair

Nadia Benkirane-Jessel

Inserm - French National Institute of Health and Medical Research, France