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 2 :

Keynote Forum

Nelson R Pinto

University of the Andes, Chile

Keynote: Transforming tissue repair into truly regeneration with L-PRF

Time : 09:00-09:40

OMICS International Tissue Science Congress 2017 International Conference Keynote Speaker Nelson R Pinto photo
Biography:

Nelson R Pinto is the Founder and Chairman of the Research Center for Tissue Engineering and Regenerative Medicine in Concepcion, Chile, where for the past 30 years he maintained an active private practice specializing in Advance Oral Implantology. Currently, he is a Professor at the Universidad de Los Andes, Chile, Post-Graduate School of and Periodontics and Implantology and a Visiting Professor at the Department of Oral Health Sciences and Periodontology, University Hospitals Catholic University, Belgium. He is a world leading expert in L-PRF, soft and hard tissue regeneration and wound healing.

Abstract:

Leukocyte/platelet-rich fibrin (L-PRF), a second-generation platelet concentrate for topical use, is an autologous blood-derived product, which can be obtained, quickly and at low cost. It is classified as one of the four families of platelet concentrates for surgical use and is, therefore, a different class of products than traditional PRPs. L-PRF is produced from peripheral, which is immediately centrifuged without any anticoagulant. Coagulation starts during the centrifugation according to a specific protocol (FDA approved and CE marking). After centrifugation a red blood cell base at the bottom, acellular plasma as a supernatant (platelet-poor plasma) and the L-PRF clot in-between can be observed. The latter, rich in fibrin, platelets (±95% of initial blood) and leukocytes (±50% of initial blood), can be transformed into a membrane of 1 mm in thickness by careful compression in a surgical box (Expression Box, IntraSpin System, Intra-lock, Boca Raton, USA). L-PRF membranes remain intact for more than 14 days in vitro (even more than 28 days in culture) and over 21 days in vivo. Due to a specific polymerization, architecture of the fibrin matrix and cell content they possess antibacterial effects. L-PRF appeared therefore as a very interesting biomaterial to enhance wound healing. As it was proven in vitro, the Intraspin/LPRF membranes with a special fibrin network, progressively release a significant amount of growth factors (e.g., transforming growth factor β1 (TGFβ-1), platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF), BMPs and insulin-like growth factors (IGF)), matrix glycoproteins (thrombospondin-1 (TSP-1)), fibronectin and vitronectin) and sequences of cytokines (e.g., IL-1β, IL-6, TNF-α and IL-4) for at least 7 days. The effects of L-PRF in vitro on cell cultures are very strong during at least 28 days, with a strong stimulation of proliferation of all tested cell lines (fibroblasts, pre-keratinocytes, preadipocytes, osteoblasts and mesenchymal stem cells) and also a stimulation of differentiation of bone cells. L-PRF membranes behave in vitro like a Human Living Tissue interacting in co-cultures with cells (with the release of the leukocytes from the membrane enhancing the environment to stimulate the M2 macrophage activity and this specific behavior reinforced the idea of using L-PRF membranes like a covering tissue graft in skin wounds. L-PRF can be considered as an autologous blood derivate living tissue graft. In this sense, L-PRF is a very simple treatment without any risk for the patient that could be tried in all cases. The possibility to use L-PRF as a biological scaffold by itself or associate with a biomimetic implant surface as open the opportunity to regenerate soft and hard tissue in such a way that was not possible before. The clinical, immune histochemistry and histological findings (SEM, Confocal Laser and Optical Microscopy) of our animals and humans studies over the last 14 years confirm the potential of L-PRF as a biological scaffold or as a living tissue graft for hard and soft tissue regeneration in acute or chronic wounds. We have been able to probe the potential of L-PRF as a regenerative biomaterial in chronic wounds such as: Diabetic foot, venous ulcers, osteomyelitis, and osteonecrosis by bisphosphonate. In acute wounds: Traumatic wounds and burns. The possibility to use L-PRF in regenerative procedures like bone or skin grafts had led to new treatment concepts affecting a broad spectrum of clinical conditions. What we thought impossible yesterday could be routine tomorrow, through the natural guided regeneration therapy with IntraSpin/L-PRF.

Keynote Forum

Debra Aub Webster

Cardinal Health Regulatory Sciences, USA

Keynote: Regulatory considerations for regenerative therapeutics: US perspective

Time : 09:40-10:20

OMICS International Tissue Science Congress 2017 International Conference Keynote Speaker Debra Aub Webster photo
Biography:

Debra Aub Webster has over 20 years of experience in pharmaceutical research and the regulatory environment. She has started her regulatory career with the US FDA as Reviewing Toxicologist/Pharmacologist. As a Principal Scientist in Regulatory Affairs and Product Development with Cardinal Health Regulatory Sciences, she leads projects for biologic and regenerative medicine product development programs. In this capacity, she provides guidance on clinical, nonclinical and regulatory aspects of strategic product development, author’s regulatory documents and acts as the Regulatory Representative for sponsors in interactions with the FDA.

Abstract:

The regulation of human cells and tissues by the United States Food and Drug Administration (FDA) originated with the 1902 Biologics Control Act and the 1944 Public Health Service (PHS) Act. These initial acts were put into place to ensure purity of serum and vaccines and to control the spread of communicable diseases, respectively. As the use of human cells and tissues has expanded, FDA was faced with the dilemma of differentiating between their uses in the practice of medicine versus in the manufacture of a product. Under the authority of Section 361 of the PHS Act, FDA introduced a comprehensive regulatory program in 1997 for human cells, tissues and cellular and tissue-based products (HCT/Ps). This consolidated regulatory approach covered all cells and tissues and was tiered and risk-based to allow for less regulatory evaluation of products determined to present a minimal risk to patient safety. In 2005, this regulatory program was implemented in rules codified under 21 CFR Section 1271. These rules defined the conditions that must be met for an HCT/P to be regulated solely under the PHS Act (called 361 HCT/Ps) and those that would be defined as biological products that would also be regulated under the Food, Drug and Cosmetic Act requiring market clearance (called 351 HCT/Ps). This determination and the potential regulatory pathways for these cutting edge technologies is often complex and understanding these regulatory pathways and the definitions surrounding them is critical to successful product development in the United States. Beyond the challenges of navigating the regulatory maze for new regenerative therapeutics, sponsors must also adopt new approaches to evaluate safety and efficacy, and to identify measurable quality attributes regarding product safety, quality and potency. FDA is actively engaged in providing guidance and expedited approval pathways in order to bring these discoveries safely forward to benefit patients.

Keynote Forum

Leah Vardy

Agency for Science, Technology and Research, Singapore

Keynote: Polyamine mediated regulation of wound healing

Time : 10:20-11:00

OMICS International Tissue Science Congress 2017 International Conference Keynote Speaker Leah Vardy photo
Biography:

Leah A Vardy is a Principal Investigator at the Institute of Medical Biology, A*STAR and an Adjunct Assistant Professor at the Nanyang Technological University in Singapore. She has received her PhD at the Imperial Cancer Research Fund in London and has completed her Postdoctoral work at the Whitehead Institute in Cambridge at the MIT, USA. She has authored over 35 peer reviewed scientific articles in a diverse array of systems including yeast, fruit flies, embryonic stem cells and epidermal cells. Her recent lab studies on embryonic stem cells were published in a series of papers. Currently she has been focusing her research on the epidermis and has been addressing the role of the polyamines in skin barrier function, wound healing and tissue repair.

Abstract:

The primary function of the epidermis is to serve as a protective barrier against the environment. Loss of skin integrity due to injuries or illness results in wounding. Wound healing is a dynamic process involving changes in gene expression on multiple levels. Here, we describe a role for AMD1 (Adenosylmethionine Decarboxylase 1), the rate limiting enzyme in the polyamine biosynthesis pathway, in wound healing. The polyamines, spermine, spermidine and putrescine are ubiquitously expressed cations that are essential for cellular function and play a role in a wide array of cellular processes. We show that AMD1 is expressed in the more differentiated layers of the epidermis and is transiently up-regulated at the wound edge in ex vivo wounded human skin biopsies. Cultured keratinocytes also showed an up-regulation of AMD1 at the wound edge in a scratch assay. Knock-down of AMD1 delayed cell migration and closure of the scratch wound suggesting that high polyamine levels are required for cell migration. We have been working to determine the downstream targets of the polyamine pathway in the wound healing response and these findings will be presented. We propose that AMD1 is an important regulator of cell migration and targets multiple pathways to promote wound healing.

  • 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.