Keynote Speaker

Diana Anderson

Biomedical Sciences, University of Bradford, UK

Title: Susceptibilities to DNA damage induced by oxaliplatin in different phases of germline stem cells

Time: 09:45AM - 10:30 AM

Diana Anderson

Biography

Diana Anderson  (H index 62) holds the Established Chair in Biomedical Sciences at the University of Bradford. She obtained her first degree in the University of Wales and second degrees in the Faculty of Medicine, University of Manchester. She has 450+ peer-reviewed papers, 9 books, has successfully supervised 32 PhDs, is an Editorial Board Member of 10 international journals. She is Editor-in-Chief of a book series on Toxicology for the Royal Society of Chemistry. She gives plenary and key note addresses at various international meetings. She is a consultant for many international organizations, including WHO, EU, NATO, TWAS, UNIDO, OECD.

Abstract

Germline stem cells are susceptible to a variety of genotoxic anticancer drugs which induce DNA damage and oxidative stress. Even low doses to the testicular cells may pose reproductive risks with possible treatment-related infertility. Germline stem cells are the cells responsible for the transmission of genetic information from an individual to the next generation. Various compounds have a negative impact on the germline stem cells, either directly, or indirectly affecting them through their action on the somatic nursing cells, mainly Sertoli cells. Ultimately, these effects can inhibit fertility, and may have deleterious consequences for the progress of the progeny. Oxaliplatin is a platinum-based anti-cancer drug with antineoplastic properties used mainly for colorectal cancer and is cytotoxic due to platinum binding to DNA and the formation of intrastrand cross-links between neighbouring guanines. The aim of the study was to examine the effects of oxaliplatin on spermatogenic cells separated using STAPUT unit-gravity velocity sedimentation. DNA damage was assessed in the Comet assay. The effects of oxaliplatin on mRNA and their proteins of  glial cell line derived neurotrophic factor receptor (GDNFR) in spermatogonia, synaptonemal complex protein 3 (SCP3) in spermatocytes and transition protein (TP1) in spermatids were also studied using quantitative polymerase chain reaction (qPCR) and Western blot methods. Results indicated that oxaliplatin induced DNA damage and significantly decreased levels of GDNFR, SCP3 and TP1 mRNA and their proteins. Spermatogonia followed by meiotically dividing spermatocytes were highly susceptible target cells.

Understanding the mechanisms of action of oxaliplatin underlying its effects in germline stem cells is an important way to examine emerging new protection strategies for the reproductive system. Thus, examining the molecular mechanisms of germline stem cells provides a better understanding of spermatogenic cell regulation.

Peter Ghosh

Biography

Professor Peter Ghosh has been engaged in medical research for more than 45 years and is an acknowledged authority on musculoskeletal disorders/diseases and modalities for their treatments and repair. He is author or co-author of over 420 publications and is inventor or co-inventor of 22. patents. From 1974 until 2002 he was Associate Professor and Director of the Raymond Purves Research Laboratories in the Department of Surgery, University of Sydney and President of the Institute of Bone and Joint Research at Sydney’s Royal North Shore Hospital from 1999 until his retirement in 2002. He is Past President of the Australian and New Zealand (ANZ) Orthopaedic Research Society and the Matrix Biology Society of ANZ and is an ex-board member of the Osteoarthritis Research Society International (OARSI) and the Bone and Joint Research Foundation of the University of Sydney. He is currently Honorary Associate Professor University of Sydney, Adjunct Professor, Institute of Medical Engineering, and the Richie Institute at Monash University, Clayton, Victoria. Australia and visiting Professor in the Faculty of Medicine, Chiang Mai University, Thailand.  He has been a consultant to the regenerative medicine company - Mesoblast Ltd since 2005 and was responsible for the development and execution of their preclinical research programs in arthritis and degenerative disc disease which have now progressed to Phase 2 and 3 human clinical trials. Since 2004 he has been CEO and Director of Proteobioactives Pty Ltd which has developed novel methodologies for the repair of musculaskeletal tissues, particularly the injured and degenerate intervertebral disc, using mesenchymal stem cells and scaffolds.

Abstract

Background
Our previous studies had demonstrated the capacity of pentosan polysulfate (PPS) to stimulate mesenchymal stem cells (MSCs) chondrogenic differentiation when cultured in-vitro (1). However, to evaluate the clinical potential of PPS treated MSCs to repair cartilage defects or degenerate discs it was critical to devise a strategy of maintaining the integrity and lifetime of MPCs at the site of injury. To achieve this goal, we first demonstrated the ability of PPS to induce MPC proliferation and chondrogenesis when seeded in collagen sponges. We next evaluated the in-vivo outcomes of this procedure with PPS treated MPCs imbedded in sponges that were deposited in Fidji cages interposed between the cervical discs of adult sheep. The positive outcomes prompted subsequent preclinical studies using an ovine model of lumbar discectomy (2,3) which confirmed the validity of this strategy.
Methods and Materials
STRO-1+ immunoselected bone marrow MSCs were injected into 4mm cubes of Gelfoam sponges cultured in DMEM+10% FBS with PPS in the absence (control) or presence of 1.0 -
20.0 ug PPS/ml. Cell viability was monitored by DAPTI staining after fixation and proliferation by 3H -Thymidine incorporation into DNA. Proteoglycan (PG) synthesis was quantified by incorporation of 35-S PGs and MPC gene expression monitored on days 7,14 and 21 using RT-PCR.
Results
DAPTI and thymidine uptake showed that MPC viability and proliferation were maintained over 21 days in the presence of PPS. DNA synthesis was maximal with 2.5 ug/mL PPS (p < 0.03) on day 10. Proteoglycan (PG) biosynthesis was PPS concentration and time
dependent. Maximal PG synthesis (82% > control, p = 0.0005) occurred with 2.5 ug/mL PPS on day 10, while 100% > control was observed on day 14 (p < 0.0001). RT – PCR determined gene expression of markers of chondrogenesis, including SOX-9, Aggrecan , type II collagen were elevated and osteogenesis markers down regulated at PPS concentrations of
2.5 -10 ug/mL.
Conclusion
These studies demonstrated the ability of collagen scaffolds to preserve and enhance the gene modifying effects of PPS on MSCs which allowed us to translate this technology to repair herniated discs in large animal models of lumbar discectomy (2,3). We now plan to translate this procedure to the human arena which currently is devoid of therapeutic modalities that encouraging disc repair following discectomy, one of the most common surgical procedures worldwide.

Magnus S. Magnusson

Biography

Magnus S. Magnusson, PhD, Research Professor, founder and director of the Human Behavior Laboratory, University of Iceland. Author of the T-pattern model, the T-system and the corresponding detection algorithms and software THEMETM (PatternVision.com), initially focusing on real-time organization of behavior. Co-directed DNA analysis. Numerous papers, talks and keynotes in ethology, neuroscience, mathematics, religion, proteomics, mass spectrometry and nanoscience. Deputy Director 1983-1988 in Museum of Mankind, National Museum of Natural History, Paris. Repeatedly invited Professor at the University of Paris, V, VIII and XIII in psychology and the biology of behavior.  Now works in formal collaboration between 32 European and American universities initiated 1995 at University of Paris V, Sorbonne, based on “Magnusson’s analytical model”.          

Abstract

Statement of the Problem: Extent and kinds of self-similarity based on T-patterns across levels of biological organization and many orders of temporal and spatial magnitude, thus aiming at new biomathematical understanding of mass-societies from protein (Cell City) to human mass-societies.

Methodology & Theoretical Orientation: Beginning in the early 1970’s this work has many roots but initially mostly in ethology (biology of behavior) and especially the work of N. Tinbergen, K. Lorenz and K. von Frisch, for which they shared the Nobel prize in Medicine or Physiology 1973. Their smallest subjects were insects. Various other influences come from linguistics, psychology, computer science, A.I. and genetics.  Essential here is the T-pattern model with corresponding search algorithms and software (THEMETM), which has allowed T-pattern detections in animal and human behavior and interactions as well as in brain cell interactions in neuronal networks . Finally T-pattern search in DNA and proteins has provided essential information leading to the concept of T-patterned physical spatial string or T-string; a physical object.

Conclusion & Significance: While temporal and spatial T-patterns appear widely, giant durable T-strings, respectively DNA and text, turn out to be essential in protein and modern human mass-societies, but in no other mass-societies in nature. Such T-string self-similarity across more than nine orders of magnitude only exists in humans, with dramatic consequences, since the appearance of writing, billions of years after the evolution of DNA in the RNA world. This biomathematical continuum from the protein world to modern mass societies and culture (including mass-religions)  provides a unified view of biology and culture, a new perspective on the recent human text-based mass-societies appearing in a biological eye-blink. Moreover, this suggests that the mathematical T-pattern and T-string models may be of considerable importance for the understanding of processes in modern human societies and in the biological cell.

Speaker

Medet Jumabay

David Geffen School of Medicine at UCLA, USA

Title: Brown Adipose Tissue is a Source of Multipotent Stem Cells with Propensity for Neurogenesis

Time: 12:30-13:00

Medet Jumabay

Biography

Dr.Medet Jumabay has been serving as a doctor and researcher in the field of cardiovascular medicine for more than twenty years. Dr. Medet Jumabay has graduated from medical school and started her medical career at the Emergency Center of the First Affiliated Hospital of Xinjiang Medical University. Later she became an attendant physician and cardiologist in the department of medicine at the same university. Dr.Medet Jumabay received her Master's degree from the Xinjiang Medical University and a PhD. degree from the Department of Medicine, Nihon University, Tokyo, Japan in medical science. Dr. Medet Jumabay first became

Fascinated by the power of cell plasticity when she saw beating cardiomyocytes, which are derived from adipose stem cells. Thus, she became interested in cell regeneration research immediately after completing her PhD. studies. In 2007, she was recruited to the Division of Cardiology, Department of Medicine, UCLA, as a researcher in the field of cardiovascular and stem cell biology.

Abstract

Adipose tissue-derived stem cells provide a stem cell source for tissue regeneration and tissue repair. We have previously shown that multipotent cells derived from white mature adipocytes, referred to as dedifferentiated fat (DFAT) cells, differentiate into multiple mesenchymal lineages including cardiomyocytes and endothelial cells. However, it is unclear whether DFAT cells from white and brown adipose tissue have similar characteristics. The high innervation of brown adipose tissue by the sympathetic nervous system and dense vascularization suggest it might be a better source of neuronal precursor cells. Thus, we hypothesize that stem cells derived from white and brown adipose tissue, respectively, differ in their ability to undergo neurogenesis. To investigate potential differences, we cultured and optimized conditions for white and brown DFAT cells in neural induction medium or regular culture medium, and compared marker expression of neural precursors, and neuronal and glial cells using fluorescence-activated cell sorting (FACS), bright-field imaging, immunofluorescence, and RNA analysis. The results showed that both brown and white derived DFAT cells were able to generate neuronal cells and glial-like cells in neural induction medium as well as in regular culture medium. The differences were dependent on culture conditions and time of neurogenic induction. Furthermore, brown DFAT cells showed enhanced neurogenesis under neurogenic conditions, whereas white DFAT cells exhibited greater potential of becoming glial-like cells under regular culture conditions. Together, our results suggest that DFAT cells derived from brown adipose tissue have a higher propensity for neurogenic differentiation and may serve as a source of neural precursor cells.

Speaker

Gerald C. Hsu

Datt Mediproducts Pvt. Ltd,India

Title: Methodology of math-physical medicine

Time: 14:00-14:30

Gerald C. Hsu

Biography

The author received an honorable PhD in mathematics and majored in engineering at MIT. He attended different universities over 17 years and studied seven academic disciplines. He has spent 20,000 hours in T2D research. First, he studied six metabolic diseases and food nutrition during 2010-2013, then conducted research during 2014-2018. His approach is “math-physics and quantitative medicine” based on mathematics, physics, engineering modeling, signal processing, computer science, big data analytics, statistics, machine learning, and AI. His main focus is on preventive medicine using prediction tools. He believes that the better the prediction, the more control you have.

Abstract

Math-physical medicine approach (MPM) utilizes mathematics, physics, engineering models, and computer science in medical research. Initially, the author spent four years of self-studying six chronic diseases and food nutrition to gain in-depth medical domain knowledge. During 2014, he defined metabolism as a nonlinear, dynamic, and organic mathematical system having 10 categories with ~500 elements. He then applied topology concept with partial differential equation and nonlinear algebra to construct a metabolism equation. He further defined and calculated two variables, metabolism index and general health status unit. During the past 8.5 years, he has collected and processed 1.5 million data. Since 2015, he developed prediction models, i.e. equations, for both postprandial plasma glucose (PPG) and fasting plasma glucose (FPG). He identified 19 influential factors for PPG and five factors for FPG. He developed the PPG model using optical physics and signal processing.  Furthermore, by using both wave and energy theories, he extended his research into the risk probability of heart attack or stroke. In this risk assessment, he applied structural mechanics concepts, including elasticity, dynamic plastic, and fracture mechanics, to simulate artery rupture and applied fluid dynamics concepts to simulate artery blockage. He further decomposed 12,000 glucose waveforms with 21,000 data and then re-integrated them into three distinctive PPG waveform types which revealed different personality traits and psychological behaviors of type 2 diabetes patients. Furthermore, he also applied Fourier Transform to conduct frequency domain analyses to discover some hidden characteristics of glucose waves. He then developed an AI Glucometer tool for patients to predict their weight, FPG, PPG, and A1C. It uses various computer science tools, including big data analytics, machine learning, and artificial intelligence to achieve very high accuracy (95% to 99%).


Speaker

Arezoo Mohammadipoor

United States Army Institute of Surgical Research, San Antonio, TX

Title: Are cell-based products safe for clinical applications?

Time: 14:30-15:00

Arezoo Mohammadipoor

Biography

TBA

Abstract

Background: Mesenchymal stem cell (MSC)-derived conditioned media (CM) and extracellular vesicles (EVs) can effectively mimic the therapeutic effects of MSCs as demonstrated in preclinical animal models. Yet, to develop safe and effective cell-free therapies, a knowledge gap needs to be addressed pertaining to safety. In this study, we assessed the thrombogenicity of CM and EVs in an ex vivo setting.

Methods: Bone marrow-derived MSCs (passage 3) from 4 human donors were incubated in serum-free medium (SFM). After 24 hours, CM was collected and EVs isolated by ultracentrifugation. Protein content of CM and EVs was evaluated using ELISA and Pierce 660-nm protein assay. Thrombogenicity was evaluated using thromboelastography (TEG) by mixing whole blood from healthy donors with SFM, CM or EVs at 1:1 and 1:10 ratios (CM: blood volume, n ? 14). Repeated measures mixed-model with Turkey’s adjustment was performed using SAS 9.4. Tests were two-sided with significance set at p<0.05.

Results: Compared to SFM, CM accelerated the duration to initial clot formation (R) at a 1:1 ratio (p<0.001), but not at the 1:10 dilution; however, there was no effect on duration to max clot formation time (K) or clot strength (MA). Compared to EV-poor (EVP) fraction of CM, R was accelerated in the EVs at both 1:1 and 1:10 dilutions (p=0.0075 and p=0.0356, respectively) with no effect on K or MA. By comparing the variability of R values in response to CM from specific MSC donors, we found a significant donor effect (p=0.0008). Finally, EV lysate from donors with significantly reduced R had a higher content of tissue factor (TF) compared to their CM and non-thrombogenic donors.

Conclusions: Cell-free products, especially EVs, may be pro-coagulant; however, their thrombogenic potency is donor dependent. Our preliminary results imply that the presence of TF in EVs may be the key factor in this effect.

Speaker

Qian Xie

Quillen College of Medicine, East Tennessee State University,USA

Title: The HGF/MET Signaling and Therapeutics in Glioblastoma

Time: 15:00-15:30

Qian Xie

Biography

TBA

Abstract

Background: Genomic profiling of glioblastoma (GBM) has identified four molecular classifications, with the mesenchymal subtype as the most invasive phenotype resulting in short survival. The Met oncogene activation leads to invasive tumor growth and is a mesenchymal marker. Within the same GBMs, elevated MET activation is often accompanied by an increased expression of hepatocyte growth factor (HGF), suggesting a ligand-dependent activation of MET via an HGF-autocrine loop formation. While we show previously that HGF-autocrine activation predicts sensitivity to MET tyrosine kinase inhibitors (TKI) in GBM, whether it is causal to glioma initiation remains elusive.

Method: Using a well-established Sleeping Beauty (SB) transposon strategy, we injected human Hgf and Met DNA together with a short hairpin siRNA against p53 (SB-hHgf/Met.shP53) into the lateral ventricle of neonatal mice to induce spontaneous glioma initiation and characterized the tumors with pathological analysis using HE and immunohistochemistry (IHC) staining. Glioma neurosphere cells were also isolated for measuring the sensitivity to a specific MET TKI.

Results: Mixed injection of SB-hHgf/Met.shP53 induced de novo glioma formation with invasive tumor growth that resembles human GBM pathology. While neural stem cells (NSC) are hypothetically considered the cell of origin of GBM, the glioma spheres harvested from the tumor models expressed nestin, GFAP, and Sox 2, the markers of NSCs. When cultured in vitro, we show that specific MET TKI inhibited HGF-autocrine neurosphere formation and downstream MET pathway activation. Conclusion: Our results suggest that constitutively MET activation by endogenous HGF overexpression may transform NSCs into glioma initiating cells, resulting in GBM formation that is sensitive to MET TKIs. Furthermore, our genetically engineered glioma mouse model driven by human HGF-autocrine activation (SB-hHgf/Met.shP53) provides a great tool for studying GBM tumor biology and MET targeting therapeutics. 

Feng Hong

Biography

TBA

Abstract

Background: Acute liver failure (ALF) is a serious threat to the life of people all over the world. It's urgent and significant to develop safe and effective therapeutic method to treatments. Human liver stem cells (HLSCs) are early undifferentiated cells that have been implicated in the regeneration and functional reconstruction of the liver. In the present study, we isolated human liver stem cells (HLSCs) from human liver tissue and evaluated the effects of HSPCs on protecting mice from immune-mediated liver injury by injection of Con A.

Methods: HLSCs were characterized by microscopy, functional assays, gene expression, and western blot analyses. We showed that HLSCs can differentiate into hepatocytes. We intraperitoneally injected HLSCs in mice and administered ConA via caudal vein injection 3, 6, 12, 24, and 48 h later. The effects of HLSCs transplantation were evaluated through blood tests, histology, and flow cytometry.

Results: We found that the mortality of mice transplanted with HLSCs was lower compared to mice injected with PBS in this model. HLSCs reduced the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in serum and dramatically decreased the severity of liver injuries. Moreover, injection of HSPCs-CM could also relieve the mortality of mice, reduce the levels of serum ALT, AST and TBIL and narrow the area of liver necrosis induced by Con A.

Mechanistically, HLSCs promoted myeloid-derived suppressor cell (MDSC) migration into the spleen and liver, while reducing CD4+ T cell levels in both tissues and HLSC-transplanted mice exhibited lower frequencies of Th17 cells and higher frequencies of Tregs in liver and spleen than mice treated with PBS after Con A injection.

In addition, HLSCs cells suppressed the secretion of proinflammatory cytokines, such as tumor necrosis factor-? (TNF-?)?interferon-? (IFN-?), but led to increased interleukin-10 (IL-10) production.

Conclusions: These results confirm the efficacy of HLSCs in the prevention of the ConA-induced acute liver injury through modulation of MDSCs and CD4+ T cell migration, and inhibiting Th17 cells differentiation and promoting Tregs differentiation, and cytokine secretion?suggesting that HSPCs can be used as a candidate and effective therapeutic method in the treatment liver injury.

Siddharth Pandey

Biography

Dr. Siddharth Pandey has completed his PhD in Biotechnology, specialized in stem cell biology and tissue engineering from Institute of Nuclear Medicine and allied Sciences (INMAS), A unit of DRDO and Jamia Hamdard. He has started his carrier at Datt Mediproducts Pvt. Ltd.  and currently, working as the Manager and Head of Department of Life Science (R&D) at Datt Mediproducts Pvt. Ltd. In his thesis work, he focused on Stem Cell Microencapsulation and its evaluation in increasing the efficiency of stem cell transplantation. His research interests lie in the area of stem cell biology, tissue engineering, neuronal tissue engineering, and cell transplantation. Apart from research, he has also very sound knowledge in Regulatory affairs, clinical research, and technology transfer and product commercialization. He has 3 international publications and he filled more than 15 patents and 4 US patents was granted.

Abstract

Chronic wounds that damage underlying skin tissues impose a significant burden on both patients and health care system. In spite of availability of various therapies, management of chronic wounds such as diabetic ulcers and burn injuries remains a great challenge due to increasing incidences resulting in high demand and poor understanding of wound healing mechanism. Severe thermal burns need critical attention and effective therapies for shock prevention and scar improvement. Mesenchymal stem cells (MSC) are an attractive option as a therapy for chronic wounds as they increase wound closure, re-epithelialization, angiogenesis, tissue formation, while simultaneously decrease inflammation, and regulate ECM remodeling; all of which are key steps in wound repair. Till 2016, there are 105 MSC-based clinical trials reported for wound healing, out of which 30 trials have been successfully completed while 75 are ongoing. According to these data, most clinical trials occur in an early phase (phase I, I/II, or II), demonstrating that therapeutic effectiveness of MSCs needs to be investigated further. The major challenges of long-term safety of MSC-based therapies that continues to pose a major limitation in translating MSCs into clinical practice have also been discussed. We have developed mesenchymal stem cells and scaffold based product and check the efficacy of product against SD rats and we found that scar free healing in animals within 14-16 days. Developed tissue has very good tensile strength and non immunogenic. Histological analysis of the tissue also supports the results.

Speaker

Alaa T. Alshareeda

King Abdullah International Medical Research Centre, Saudi Arabia.

Title: Mesenchymal stem cells; the knife cuts on both sides of breast cancer

Time: 17:00 -17:30

Alaa T. Alshareeda

Biography

Dr. Alshareeda current research interests include the therapeutic potential of Mesenchymal Stem Cells (MSCs) in treating breast cancer, fabrication of cell sheet and biodegradable scaffolds. Dr. Alshareeda completed her Ph.D. at Nottingham University, Nottingham, UK, focusing on the assessment of DNA-Double Strand Break Repair (DSBR) in breast cancer and received a BSc degree of Biochemistry form King Saud University, Riyadh, Saudi Arabia. She completed her postdoctoral research program at Tokyo Women Medical University (TWMU), Tokyo, Japan in TWMU, exploring the potential of MSCs on the development of Hepatocellular Carcinoma using cell sheet. She has collaborated actively with researchers in several other including Nebraska University (USA), and TWMU Tokyo, Japan.

Abstract

Mesenchymal stem cells (MSCs) can influence the tumor microenvironment (TEM) and play a major role in tumourigenesis. Triple-negative [Estrogen receptor (ER-), Progesterone receptor (PgR-), and HER2/neu receptor (HER2-)] breast cancer (TNBC) is an aggressive class of BC characterized by poor prognosis and lacks the benefit of routinely available targeted therapies. This study aims to investigate the effect of human placental chorionic villi derived MSCs (CVMSCs) on the behavior of TNBC in vitro. This was done by assaying different cancer hallmarks including proliferation, migration and angiogenesis. Cell proliferation rate of TNBC cell line (MDA-MB231) was monitored in real time using the xCELLigence system. Whereas, Boyden chamber migration assay was used to measure MDA-MB231 motility and invasiveness toward CVMSCs. Finally, a three-dimensional (3D) model using a co-culture system of CVMSCs with MDA-MB231 with or without the addition of human umbilical vein endothelial cells (HUVECs) was created to assess tumor angiogenesis in vitro. CVMSCs were able to significantly reduce the proliferative and migratory capacity of MDAMB231 cells. Co-culturing of MDA-MB231 with CVMSCs, not only inhibited the tube formation ability of HUVECs but also reduced the expression of the BC characteristic cytokines; IL-10, IL-12, CXCL9 and CXCL10 of CVMSCs. These results support the hypothesis that CVMSCs can influence the behaviour of TNBC cells and provides a basic for a potential therapeutic approach in a pre-clinical setting. The data from this study also highlight the complexity of the in vitro cancer angiogenesis model settings and regulations.

Keynote Speaker

Bruce K. Young

New York University School of Medicine, USA

Title: Clinical Potential of Human Amniotic Fluid Stem Cells

Time: 10:00-10:45

Bruce K. Young

Biography

Dr. Young is the Silverman Professor of Obstetrics and Gynecology at the New York University School of Medicine.  He is internationally known as a leader and innovator in Obstetrics and Gynecology.   He introduced prenatal genetic diagnosis and performed the first amniocenteses at the NYU Medical Center, founding the Prenatal Diagnosis program in 1972 and the Division of Maternal-Fetal Medicine in 1975. Other innovations followed, including fetal heart rate monitoring, continuous fetal scalp blood pH measurements in labor, universal umbilical artery and vein blood testing at birth, intravenous infusion of magnesium sulfate for pre-eclampsia instead of an intramuscular injection, the world’s first Obstetrical Intensive Care Unit, and a technique for fetoscopic closure of preterm ruptured membranes.  Dr. Young has published 130 peer –reviewed papers, edited 2 books on Maternal-Fetal Medicine and written 2 books for the general reader.  He is emeritus Director of the Division of Maternal-Fetal Medicine at the NYU  Lang one Health Center, and is a member of the Kimmel Stem Cell Center there.  His current research focuses on human amniotic fluid derived stem cells.

Abstract

Background:

Stem cells, undifferentiated cells with ability to self-replicate without differentiation, have great therapeutic potential for genetic and autoimmune disease, malignancies and even whole organ replacement. Currently, stem cells sources include bone marrow, peripheral blood, umbilical cord cells, umbilical cord blood, induced pluripotent cells and embryonic tissue. Each of these sources has limitations. Amniotic fluid stem cells (AFSC) collected in the first half of pregnancy have been identified as a source of stem cells with possible therapeutic potential. Our lab recently has shown that term AFSC has similar characteristics to early AFSC. The objective was to characterize AFSC, specifically confirm potential for differentiation and clinical potential.

Methods:

Amniotic fluid was collected from uncomplicated pregnant women at indicated midterm amniocentesis and at scheduled, term, cesarean delivery. Samples from the genetics lab after culture, and fresh samples were cultured and underwent cell expansion, and aliquots were frozen. Cell viability and proliferation studies were performed. Flow cytometry was used to identify surface markers associated with stem cells, including SSEA-4, CD-90 and TRA-1-60. AFSC were differentiated toward neural lineage and monoclonal antibodies for Nestin, B-tubulin III and glial fibrillary acidic protein (GFAP) used to confirm differentiation by fluorescent microscopy. AFSC were differentiated toward osteocyte lineage and stained for presence of alkaline phosphatase-producing cells, and stained with Alizarin Red solution, to confirm differentiation to osteocyte lineage by bright-field and phase-contrast microscopy, respectively. Differentiation of AFSC to chondrocytes was performed and monoclonal antibodies for aggrecan were used to confirm differentiation.

Results:

Amniotic fluid was collected from 37 midtrimester and 8 term women with mean age of 33.9 years (SD 2.7). Volumes up to 100 ml were easily collected at term, compared with 5 -15 ml at midtrimester.  All samples grew in culture with mean cell viability of 80% (SD 7%), and cell counts of 1.3 x 105 to 1.5 x 106 at term, compared to 70 -100 x 103 at midtrimester.. Proliferation studies revealed a mean doubling time of 27 hours.  AFSC were able to tolerate 10 passages without significant changes, and cry storage for up to 18 months, without loss of viability. All cells demonstrated surface markers associated with stem cells. All samples demonstrated differentiation into neural, osteocyte and chondrocyte lineages.
Conclusion:

AFSC collected at term cesarean delivery demonstrate characteristics similar to mid-trimester AFSC. Cells are able to be cultured and withstand cry storage. AFSC can be differentiated into multiple cell lineages.  AFSC may represent a readily available abundant source of stem cells for therapeutic potential and warrant further study.

Keynote Speaker

Khalid Shah

BWH /Harvard Medical School Boston, USA

Title: Next Generation of Cell based Therapies for Cancer

Time: 10:45-11:30

Khalid Shah

Biography

Dr. Khalid Shah the Director of Center for Stem Cell Therapeutics and Imaging at BWH/ Harvard Medical School. He is also the Vice Chairman of Research and Co-Director for joint Center of Excellence in Biomedicine at BWH Harvard Medical School. Dr. Shah and his team have pioneered major developments in the stem cell therapy field, successfully developing experimental models to understand basic cancer biology and therapeutic stem cells for cancer. Dr. Shah's work has caught the attention in the public domain and as such it has been highlighted in the media world-wide including features on BBC, Fox news and CNN. Dr. Shah holds current positions on numerous councils, advisory and editorial boards in the fields of cell therapy and oncology. In an effort to translate the exciting therapies develped in his laboratory into clinics, he has founded biotech companies whose main objective is the clinical translation of therapeutic cells in cancer patients.

Abstract

Cell based therapies are emerging as a promising strategy to tackle cancer. We and others have developed tumor cell surface receptor targeted adult stem cells, cancer cells and T cells expressing novel bi-functional immunomodulatory proteins and oncolytic viruses. Using recently established invasive, recurrent and resection models of primary and metastatic tumors that mimic clinical settings, the efficacy of engineered stem cells has been explored extensively. These studies demonstrate the strength of employing engineered cell based therapies in preclinical-therapeutic tumor models and form the basis for their clinical translation. This presentation considers the current status of Cell-based treatments for cancer and provides a rationale for translating the most promising preclinical studies into the clinic.

Keynote Speaker

Yong Zhao

Hackensack University Medical Center, USA

Title: Stem cell educator therapy and type 1 diabetes: from bench to clinic

Time: 11:30-12:45

Yong Zhao

Biography

Yong Zhao MD, PhD, is an Associated Scientist in the Department of Biomedical Research at Hackensack University Medical Center in New Jersey. Abnormalities in multiple immune cells and the deficit of insulin-producing cells are two crucial common issues in type 1 diabetes (T1D) and T2D. Insulin therapy is not a cure. In search of a cure for T1D, I discovered cord blood-derived multipotent stem cells (CB-SC) in 2005 and successfully translated this finding into clinical use. My colleagues and I invented Stem Cell Educator therapy for the treatment of diabetes and other autoimmune diseases in humans. Stem Cell Educator therapy is a closed-loop system that circulates the patient’s immune cells, briefly co cultures them with adherent CB-SCs in vitro, and returns only the “educated” autologous immune cells into the patient’s circulation. This groundbreaking T1D study was recognized by the American Diabetes Association at the 72nd Scientific Sessions in Philadelphia in 2012 as one of eight major diabetes breakthroughs that year.

Abstract

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes the deficit of pancreatic islet ? cells. A true cure has proven elusive despite intensive research pressure by using conventional approaches over the past 30 years. The situation highlights the challenges we face in conquering this disease. We established the Stem Cell Educator therapy by using cord blood-derived multipotent stem cells (CB-SCs). A closed-loop system that circulates a patient’s blood through a blood cell separator, briefly co-cultures the patient’s lymphocytes with adherent CB-SCs in vitro, and returns the educated lymphocytes (but not the CB- SCs) to the patient’s circulation. Our clinical data reveal that Stem Cell Educator therapy functions as “an artificial thymus” that circulates a patient’s blood through a blood cell separator, briefly co-cultures the patient’s lymphocytes with CB-SCs in vitro, induces the immune tolerance through the action of AIRE (autoimmune regulator expressed by CB-SCs), returns the educated lymphocytes to the patient’s circulation, and restores the immune balance and homeostasis. During this procedure, both peripheral and pancreatic infiltrated autoimmune memory T cells can be isolated by a blood cell separator and treated by CB-SCs. This treatment leads to the global immune modulations and immune balance as demonstrated by clinical data.  A single treatment with Stem Cell Educator provides lasting reversal of autoimmunity that allows regeneration of islet ? cells and improvement of metabolic control in T1D subjects with long-standing clinical effects. Mechanistic studies demonstrated that platelets and their released mitochondria display immune tolerance-associated markers contributing to the therapeutic effects of Stem Cell Educator therapy. Using freshly isolated human pancreatic islets, ex vivo studies established that pancreatic islet ? cells can be reprogrammed to proliferate while maintaining good cell viability and restoring normal ?-cell function after the treatment with platelet-derived mitochondria. Thus, Stem Cell Educator therapy may revolutionize regenerative medicine and mitigate safety and ethical concerns associated with conventional approaches that involve the transplantation of insulin-producing cells or the viral/drug-induced transduction of pancreatic cells or the stem cells, leading to the development of novel treatments for T1D and other autoimmune diseases in humans.

Speaker

Sandeep Shrivastava

Datta Meghe Institute of Medical Sciences, (DU) Wardha, India.

Title: Tissue Regeneration – A Possibility of Gangrene Reversals in Clinical management of wounds

Time: 12:45-01:15

Sandeep Shrivastava

Biography


Abstract

Complex wounds are many times associated with severe ischemia and infections, leading to further tissue necrosis and gangrenes. PRP as a regenerative medicine product is being studied widely for different clinical applications including for wounds, fracture impairments, tendinopathies, osteoarthritis etc.

This is based on its rich content of growth factors which triggers, promotes tissue regeneration and further healing.

At our Centre, a protocol for treatment of wounds by PRP known as Sandeep’s Technique for assisted regeneration of skin (STARS therapy) have been developed and applied for treatment of different wounds including complex wounds with infections, recalcitrant ulcer, deep with exposed tendons, bones etc. During this study, we have extended the usage to include few very challenging situations which included wounds associated with huge necrosis or limbs with impending with gangrene. They were associated with clinical signs of limb ischemia and had necrotizing skin, tendons, bones etc. exposed in the wounds. The results are very encouraging leading to the tissue regeneration in such wounds with minimum residual tissues necrotizing. Complete healing of wounds was achieved in most of them. The PRP led regeneration and the solutions being developed are indicative of revolutionary clinical outcomes, which otherwise is not a possible through current traditional pharmaceutical / surgical based therapies.

Speaker

Ellie Okada

Boston Cancer Policy Institute, USA

Title: Transnational and Comparative Dimensions of Stem Cell Science Policy

Time: 14:00-15:00

Ellie Okada

Biography

Ellie Okada is an academic, whose research and teaching interests are in governance for responsible innovation, frameworks of governance and management of knowledge-intensive organizations (such as academic institutions and multilateral organizations), and intellectual property. Former visiting scholar at Harvard University’s Weather head Center for International Affairs (August 2009-August 2010) and Columbia Business School (April 2008-August 2010), tenured full Professor at a research university in Japan (Yokohama National University) from April 1988 to March 2012 (April 1990-March 2003: Associate Professor with tenure; April 2003-March 2012: full Professor with tenure). Currently working for a nonpartisan, independent research institute of new social sciences, Boston Cancer Policy Institute, as a Senior Fellow (April, 2012-present). At the institute, Okada conducts scholarly research on governance, management, and social science aspects of translational science. Okada has 144 publications including 4 single-authored books.  As post-university activities, Okada’s experiences include an expert of a kick-off meeting of a policy project, New Sources of Growth: Knowledge-based Capital, at the Directorate of Science, Technology, and Innovation, OECD (Organization for Economic Cooperation and Development, headquartered in Paris), held in Washington, D.C.

Abstract

[Research questions] This study examines (i) factors that shape transnational or state-centered zones of stem cell research policies and (ii) how these factors affect translation pathways of academic institutions. The zones are jurisdictional fields of technologies and knowledge that regulators attempt to define (Barry, 2006; Faulkner, 2009). As debates have shifted from morality issues to applications in the stem cell science, it is a legitimate timing to reflect these questions.

[Methodology] The study conducts an inductive-deductive analysis by combining the factor analysis and in-depth case analysis. Factors investigated are institutional legacies (Banchoff, 2005, 2011; Gottweis, Salter, & Waldby, 2009; Holge, 2014), intellectual property regulations (Magnus, Caplan, & Macgee, 2002) and the competition style of moral-based stakeholders (Attas, 2004). Data sources are Lijphart’s indexes of patterns of democracy, laws and research policies of 22 OECD countries, and publicly available documents.

[Results and Discussion] Among factors of reduced variables, “the political legacy” and its constituent, “the interest group competitiveness” yield a consistent meaning (Table 1). Among countries investigated, the USA and Germany have similar legal legacies and different stem cell research policies. The in-depth analysis shows that the turning points are scientific evidence on the potential therapeutic development and rights-based arguments on the reproductive justice (see, Gottweis et al., 2009). As the distinction between the cells and organisms that have a self-directing capacity (George & Tollefsen, 2008) was not necessarily clear, the debates invited the political polarization. The prominent academic institutions complement missing elements in the translation through global research alliances.

[Conclusion] (a) Given similar legal legacies, the ambiguity in defining thresholds of cells and organisms that relate to human identity invites politics. Competition styles of moral-based stakeholders affect zones of science. (b) Societal justification affects the translational pathways of academic sciences. (c) Global research alliances complement missing factors for each other

Speaker

Fikile M. Mnisi

Tshwane University of Technology South Africa

Title: A Normative Case for the Patentability of Human Embryonic Stem Cell Technologies

Time: 15:00-15:30

Fikile M. Mnisi

Biography

Dr. Fikile Muriel Mnisi is a hospital board member at Eden vale Hospital, Johannesburg. She is a member of the International Ethics in Education Association, as well as an organizing member of the 6th International Conference in Ethics Education (IAEE), Stellenbosch (October 3-5, 2018). She is an ethics educator in association with Tshwane University of Technology and University of South Africa’s (UNISA) ethics educators program. She recently voluntarily drafted and presented (or trained) an Ethics Training Program for offenders at the Johannesburg Correctional Service under Ms Janeen Prinsloo’s Ph.D. research study. The program focused on rehabilitating offender’s moral development and ethical decisions making. Her interest are in the field of policy development (science and/ or healthcare), ethics education and research, IPR and patent ELSI matters, moral developments’ in using technology, and  social justice and access to healthcare particularly in advanced therapies and medicines or medical devices.

Abstract

We have seen exponential growth and advancement within science and technology in fields such as human genome mapping, pre-natal genetic testing and stem cell research. All these advancements in technology have given rise to ethical concerns and have often necessitated legal and social reforms. Contentious issues have brought about ethical and social unease. One example of this relates to intellectual property rights (IPRS) and their application to human tissue, through the patenting of human Embryonic Stem Cell (hESC) lines and the methods utilised to produce them. Whilst such objects meet the legal criteria for patentability in many jurisdictions, many question whether this is ethically justifiable. However, in contrast to this, concerns about the morality of patenting stem cells have resulted in legal prohibitions that have slowed or even halted research progress, as in the case of the decision of the Court of Justice of the European Union (example: Brüstle vs. Greenpase case) to ban such patents. Patent legislation and regulations have been reported to slow down scientific progress and act as a barrier to access to essential medicine and therapies (WTO, WIPO, WHO 2013). This raises another set of ethical issues, since, unless the grounds for prohibiting such patents are sound, the prohibition might be construed to be unethical in itself, as it could hamper important research that could improve the health and lives of many people. Drawing primarily on Ethics of Responsibility by Hans Jonas, I argue that the grounds for banning hESC patents are not ethically justifiable. I defend the claim that the legal principles for establishing patentability should be reformed to allow for such patents.

Speaker

Jiren Zhang

Guangdong Institute of Target Tumor Intervention and Prevention, P.R.China

Title: Application of biological age assessment of Chinese population in potential anti-ageing technology

Time: 15:30-16:00

Jiren Zhang

Biography


Abstract

This study aimed to construct a biological age assessment formula for the Chinese population and to explore the effectiveness of double filtration plasmapheresis for anti-ageing and longevity.


Methods: 915 subjects were recruited, including 584 (63.8%) males and 331 females (36.2%). Male age was 50.94±10.60 (mean±SD), and female age was 51.20±11.84 (mean ±SD). 34 blood markers were detected in the laboratory. The ageing biomarkers were determined by statistical correlation analysis and redundancy analysis, and the biological age assessment formula was established by multiple linear regression analysis. Paired sample T test was used to analyse the elimination effect of double filtration plasmapheresis on aging biomarkers.


Results: Based on the comprehensive blood test and analysis, the ageing biomarkers were screened, and the male and female biological age assessment formulas were established. Then, the elimination of ageing biomarkers by double filtration plasmapheresis was examined. Double filtration plasmapheresis can eliminate ageing biomarkers, with an average of 4.47 years decrease in age for males and 8.36 years for females.


Conclusion: So, biological age provides a scientific tool for assessing ageing, and double filtration plasmapheresis is safe and might be effective for anti-ageing and longevity. However, the effect of plasmapheresis is expected to be transient, so further studies are needed to plan the number and range of the plasmapheresis procedures necessary to consistently lower the parameters under study.

Chen Dongfeng

Biography

Chen Dongfeng is the academic leader of The Research Centre of Integrative Medicine in  Guangzhou University of  Chinese Medicine. He has his expertise in searching small molecule of Chinese medicine which regulates miRNA. Several patents have been attained in the past few years, such as the application of camphor in the preparation of Chinese medicine for preventing and controlling ischemic stroke. The main direction of recent research is the mechanism of bone marrow mesenchymal stem cells induced chondrogenic differentiation which were regulated with microRNA. The foundation of research is based on basic theory of Chinese medicine combining modern molecular biology techniques.

Abstract

Statement of the Problem: Osteoarthritis (OA) is the most common joint disease with an age-associated increase in both incidence and prevalence around the world. Clinical and epidemiologic research is crucial to understand the risk factors to diseases, find the best treatments for patients and identify therapies to prevent disease progression. However, it is not well-known about the role of microRNAs (miRNAs) and RNA editing involved in Chondrogenic differentiation in these diseases. Here, we established a Chondrogenic differentiation model induced by differentiation induction medium or small molecular of Chinese medicine to investigate the function of miRNAs and RNA editing. Methodology & Theoretical Orientation: A variety of experimental models of osteoarthritis (OA) have been tested, and find the effects of miR-181a-5p on articular cartilage degeneration. Histopathological analysis was used to detect the OA catabolic markers and microRNAs. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression. Findings: The microarray analysis and real-time reverse transcription polymerase chain reaction (RT-PCR) showed that miR-181a-5p reduced significantly in the induced group in vitro experiment. In addition, we found the adenosine deaminase acting on RNA enzymes (ADAR2 )which increased obviously in the chondrogenic induced group. Conclusion & Significance: The global expression profile of miRNAs involved in the Chinese medicine active ingredient induced chondrogenic differentiation of BMSCs have been revealed. Our study provided a foundation for future investigations of miRNA interaction networks to completely illuminate the regulatory role of small molecular of Chinese medicine in BMSC chondrogenic differentiation.

Speaker

Hulya Bukulmez

Case Western Reserve University, Cleveland, Ohio .

Title: Treatment of Lupus with Primed Mesenchymal Stem Cells: Lessons from Animal Models.

Time: SCFC 02

Hulya Bukulmez

Biography


Abstract

Systemic Lupus Erythematosus (S LE) is an autoimmune inflammatory disease that effect multiple organs with severe inflammation causing organ damage. Repair of immune regulation of the microenvironment is required to prevent terminal organ damage. In addition to B cell, T cell and Dendritic Cells functional abnormalities, Type I interferon immune pathway abnormalities and the number and functions of the T regulatory cells have been listed as abnormalities in human SLE .

Current available therapy options that do not encompass cellular treatment are not efficient in controlling disease activity and end - stage organ failure .With their immune regulatory actions, mesenchymal stem cells (MSCs) are Suggested to be an attractive alternative treatment. Unlike hematopoietic stem cells, exogenously introduced human mesenchymal stem cells MSCs (hMSCs) have not been observed to produce any major adverse effects or rejection reactions.

Although hMSC -based therapies have been shown to be feasible and safe, their secondary clinical efficacy remains an unresolved issue due the large variability of results. There are always non - responders among patients and other animal donors that receive the hMSC treatment. Discrepancies in these results are suggested to be due to both donor -to -donor variability in the immune -modulatory characteristics as well as the heterogenic nature of different MSC culture techniques.

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