Day 1 :
Weill Cornell Medical Center, USA
Time : 09:00-09:40
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.
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.
Inserm - French National Institute of Health and Medical Research, France
Time : 09:40-10:20
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.
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.
Asia Cosmetic Hospital, Thailand
Time : 10:20-11:00
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.
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.
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.
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.
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.
- Regenerative Medicine | Stem Cell Therapy | Tissue Engineering
Weill Cornell Medical Center, USA
Inserm - French National Institute of Health and Medical Research, France
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.
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.
I.M. Sechenov First Moscow State Medical University, Russia
Time : 11:40-12:00
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.
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.
LLC Chromsystemslab, Russia
Title: Mass spectrometry in regenerative medicine to promote translational resources to be implemented into personalized heathcare
Time : 12:00-12:20
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.
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.
3D Bioprinting Solutions, Russia
Title: Scaffold-free, label-free and nozzle-free biofabrication technology based on magnetic levitational assembly
Time : 12:20-12:40
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.
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.
I.M. Sechenov First Moscow State Medical University, Russia
Time : 12:40-13:00
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).
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.
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
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.
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.
I.M. Sechenov First Moscow State Medical University, Russia
Time : 14:20-14:40
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.
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.
- Special Session
IRSN- Institute of Radioprotection and Nuclear Safety, France
Time : 15:00-15:45
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 Cells, World Journal of Gastrointestinal Surgery, World Journal of Radiology, The Open Gene Therapy Journal and Journal of Clinical Rehabilitative Tissue Engineering Research.
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
National University of Singapore, Singapore
Title: Integrative approaches through transcriptome profiling to identify subset-specific gene activity in myeloma
Time : 15:45-16:05
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.
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.
Duke–NUS Medical School, Singapore
Time : 16:05-16:25
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.
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.
University of Cape Town, South Africa
Title: A 3D investigation of islet vasculature in a regenerating rat pancreas after 90% partial pancreatectomy (PPX)
Time : 16:25-16:45
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.
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.
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
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.
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.