Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 7th Annual Conference on Stem Cell and Regenerative Medicine Manchester , UK.

Day 1 :

OMICS International Stem Cell Congress 2016 International Conference Keynote Speaker Barritault Denis photo
Biography:

Denis Barritault has graduated in Physics and completed his PhD in Biochemistry from Paris University, France. He has received his Postdoctoral studies in Molecular Immunology at Pasteur Institute and NYU and as NIH Fogarty Fellow he has joined INSERM unit in Paris as Developmental Biologist. He made the first description and patents of FGF extracted from retina in 1979 and 1982 as skin and cornea healing agent and became full Professor at Paris-Est University in 1985. He has also Founded and Directed a CNRS Laboratory on cell and tissue regeneration until 2003. He is currently a President of OTR3, Emeritus Professor,Honorary Director of CRRET CNRS unit and is the author in over 200 publications and 30 patents.

Abstract:

Heparan sulfates (HS) are key elements of the extracellular matrix (ECM), which store and protect various cell communication peptides (CCP). HS play a central role in tissue homeostasis, by modulating the bioavailability of CCP hence controlling the cell migration and differentiation required for healing processes. Tissue injury will lead to destruction of cells and surrounding ECM is destroyed. CCPs synthesized by inflammatory and circulating cells can then promote tissue repair but with a loss of tissue quality, leaving scars or fibroses. We have engineered biodegradable nano-polymers mimicking the HS. They bind to the structure proteins of the damaged ECM and to the CCP produced by healthy neighboring cells, thereby restoring the ECM microenvironment and tissue homeostasis. This matrix therapy approach has considerably improved the quality of healing in various animal models with reduction or absence of fibrosis resulting in a real regeneration process. These HS mimetics have therefore been named RGTA, for ReGeneraTing Agents. The RGTA technology has been validated in over 80 published preclinical studies and is now marketed as a human healing agent both for corneal and skin ulcers. RGTA are in development for more tissue injuries including mucosis, tendon and muscle. Altogether this study underline the potential of RGTAs as a new therapeutic class in the field of regenerative medicine, simple safe and exploiting our natural potential without need for exogenous cells supply but can combine with cell therapy to restore cellular microenvironment and favor homing.

Keynote Forum

Y James Kang

Sichuan University, China

Keynote: Rejuvenation therapy for ischemic heart disease

Time : 10:00-10:25

OMICS International Stem Cell Congress 2016 International Conference Keynote Speaker Y James Kang photo
Biography:

Y James Kang is currently a Professor and Director of the Regenerative Medicine Research Center at Sichuan University West China Medical College, the President and CEO of Sichuan 3D Bio-printing Institute, the Director of Sichuan Regenerative Medicine Research and Technology Center, the Editor-in-Chief of the journals Cardiovascular Toxicology and Regenerative Medicine Research and the Editor of the book series of Methods in Pharmacology and Toxicology. Prior to his current positions, he was a Professor and Distinguished University Scholar at University of Louisville, USA (1996-2009). He was elected as a Fellow to the Academy of Toxicological Sciences in 2001. His research interests are in regenerative medicine, focusing on 3D bio-printing and cardiovascular regeneration as well as dietary manipulation of cardiovascular disease, liver fibrosis and cirrhosis, oxidative stress and antioxidant mechanisms and non-human primate models
for human diseases.

Abstract:

Cell-based therapy for ischemic heart disease holds a promise for the management of the disease condition. However, controversies regarding the eventually clinical benefits often arise from experimental and clinical studies. Unmatched conditions between experimental animal studies and clinical trials and the distinction between acute and chronic heart disease are major attributable factors to the controversies. Most experimental studies are carried out in young and healthy animals but clinical patients are often elders with multiple complications. Under acute ischemic heart disease conditions, freshly injured heart tissue may retain the potential for recovery. But under chronic conditions, the progressively deteriorative milieu dampens the repair mechanism, eliminating the tissue injury signals and diminishing the rejuvenation capacity. Therefore, reestablishing tissue injury signaling system and remobilizing the rejuvenation capacity would greatly enhance the efficacy of cell-based therapy for ischemic heart disease. To achieve this goal, we developed an approach to activate the tissue injury signaling system in the cardiac ischemic infarct tissue of Rhesus monkeys, reestablishing mesenchymal stem cell homing process and reacting myocardial repair mechanism. This approach, in combination with our recently established 3D bio-printing program, significantly improved the disease condition of heart failure in monkey model of myocardial ischemic infarction.

Keynote Forum

Taihua Wang

Interventional Hospital of Shandong Red Cross Society and Cell Biotechnology Co. Ltd, China

Keynote: Significant physical function improvements of 3 serious injured patients after neural stem cell therapy

Time : 10:25-10:55

OMICS International Stem Cell Congress 2016 International Conference Keynote Speaker Taihua Wang photo
Biography:

Taihua Wang has completed his MD in 1983 from Shandong Medical University and obtained his Postdoctoral studies in Danish Royal Hospital from 1990 to 1993.He is the Director of Interventional Hospital of Shandong Red Cross Society, one of the top hospitals in China. He has published more than 20 papers in reputed journals and was awarded 7 national patents. He is pioneer of stem cell therapy in the world and has extensive collaborations with Harvard Medical School, University of Pennsylvania, etc. He has already performed several thousand clinical cases with  during the past 12 years.

Abstract:

Here, we reported three patient cases in which they were seriously injured by accidents. Among them, two of them were injured by car accidents and the third patient was injured by falling down from Chinese house roof approximate 3 meter high, respectively. The common symptoms of them are head and chest vertebral injury, coma and incontinence of feces and pee, numbness of lower limb and disabled or restricted movement and so forth. After regular treatments at hospitals for different periods, all of them only obtained minor function recoveries. After subsequent 2 or 3 courses of treatment with neural stem cells, significant physical function improvements were successfully achieved. These functional recoveries included feeling strong waist, sitting up freely but cannot stand, perceiving feces and pee but cannot control, the left leg can move horizontally but cannot lift up, the right leg can lift up but cannot resist the resistance, higher double lower limb muscle tensions, having feeling obstacle under xiphoid process and the double arms can move freely, etc. More importantly, after stem
cell transplantation therapy, one of them, could crawl and even could walk with the help of walking aid. These preliminary clinical trials vividly demonstrated that the feasibility of stem cell therapy for the patients with serious brain and spinal cord injuries and provided pioneer evidences for further clinical trials with various stem cells to treat different human diseases.

  • Stem Cell | Stem Cell Therapy | Stem Cell Technologies
Location: Stable Room

Chair

Barritault Denis

OTR3, France

Co-Chair

Raphael Gorodetsky

Hebrew University Medical Center, Israel

Speaker
Biography:

Andrew Mearns Spragg is the Co-Founder and CEO of Jellagen Pty Ltd. He has gained a first class honors Degree in Microbiology and a PhD in Marine
Biotechnology from Heriot-Watt University, UK. For the past 16 years his career has focused on the creation of companies involved with the commercial exploitation of marine based science and technologies. He has successfully risen over £12.5M in equity finance and has secured competitive grant funding from EU and UK sources worth >£2M. He was the recipient of the 2007 Gannochy Medal from the Royal Society of Edinburgh and his entrepreneurial achievements were recognized through winning the Ernst & Young Entrepreneur of the year 2008 in Health Care for Scotland. He holds honorary chairs from the University of Stirling and Fellowships from the Royal Society of Chemistry and Biology.

Abstract:

Jellagen Pty Ltd (JPL) founded in August 2013, is a Med-Tech business exploiting jellyfish to provide the next generation of collagen biomaterials that are safer and more technically versatile than current sources of mammalian derived collagen products for application in 3D cell culture (in vitro diagnostics, including research level regenerative medicine R&D) and medical devices. JPL’s research grade materials are on market and our vision is to be the leading provider of medical grade nonmammalian collagen products to these markets in addition to conducting in-house development of new medical devices for wound and cartilage repair. Jellagen offers the following next generation collagen products for research application: Research grade acid and enzyme soluble and powdered native collagen; Collagen sponge scaffolds for 3D cell culture; Hydrogels (3D cell culture and tissue engineering application) and; Prototype bio-mimetic collagen membrane medical device products (at pre-clinical stage).

Verdon Taylor

University of Basel, Switzerland

Title: Regulation of hippocampal neural stem cell fate
Speaker
Biography:

Verdon Taylor is Professor of Embryology and Stem Cell Biology in the Department of Biomedicine of the University of Basel, Switzerland. His group studies neural stem cell maintenance and differentiation. Using genetic approaches, he addresses the signaling mechanisms that regulate neurogenesis during development and in the adult mammalian brain. In addition; he is interested in the role of endogenous stem and progenitor cells in brain tumor formation and in niche pathways that are potentially hijacked by tumor initiating cells. He has published more than 50 original papers in the area of stem cells.

 

Abstract:

Multi-lineage neuronal, astrocytic and oligodendrocytic potential is a cardinal neural stem cell (NSC) trait. In the neurogenic zones of the adult mouse brain, NSCs in the sub-ventricular zone generate oligodendrocytes as well as neurons and astrocytes. In stark contrast, NSCs in the adult hippocampal dentate gyrus (DG) generate only granule neurons and astrocytes but never oligodendrocytes in vivo. It remains unclear how this cell fate restriction is controlled. Interestingly, DG NSCs also fail to generate oligodendrocytes in vitro suggesting that they have an intrinsic fate restriction. We have studied this fate restriction of DG NSCs and identified a novel cell intrinsic mechanism controlling NSC maintenance, neurogenesis and gliogenesis in the hippocampus in vivo and of DG NSCs in vitro. I will discuss our findings about how directed mRNA stability changes DG NSC fate and controls the production of oligodendrocytes. These findings have major implications not
only for the cell fate determination of NSCs and potentially other stem and progenitor cells outside the nervous system but also for therapeutic intervention for regulated cell replacement.

Brian M. Mehling

Blue Horizon International LLC, USA

Title: Stem cell therapy for arthritis and joint injuries
Speaker
Biography:

Brian M Mehling is a practicing American Orthopedic Trauma Surgeon, Researcher and Philanthropist. He has started his path in Medicine through undergraduate study at Harvard University, obtaining Bachelor of Arts and Master of Science degrees in Biochemistry from Ohio State University. He has received his Postgraduate education through residencies and fellowships at St. Joseph’s Hospital in Paterson, NJ and the Graduate Hospital in Philadelphia, PA. While pursuing PhD in Chemistry, he operates his own practice, Mehling Orthopedics, in both West Islip, NY and Hackensack, NJ.

 

Abstract:

Musculoskeletal conditions are the most common cause of severe long-term pain and physical disability and they affect hundreds of millions of people around the world. Osteoarthritis (OA) is the most common form of arthritis and the leading cause of chronic disability. OA is estimated to affect 630 million people worldwide. OA is characterized by degeneration of articular cartilage, limited intraarticular inflammation with synovitis and changes in peri-articular and subchondral bone. BHI Therapeutic Sciences offers a novel method of arthritis therapy using a patient’s own stromal vascular fraction (SVF) cells
including mesenchymal stem cells. The therapy is available at Malacky Hospital in Slovakia. Malacky Hospital is staffed with expertly-trained medical professionals and is one of the premiere hospitals in Central Europe. Blue Horizon International Slovakia is licensed by the Ministry of Health of Slovak Republic to provide adipose stem cell treatments for orthopedic joint applications - knees, hips, shoulders, and ankles. Procedures utilize cutting-edge technology and adult stem cells only. In 2015, 73 patients underwent the therapy with own stromal vascular fraction cells. 64 patients have follow-up evaluation results. Affected area includes knees (37 patients), hips (25 patients), hips and knees (2 patients). Results from patients’ follow-up
examinations and MRI scans showed that stem cell therapy was safe for the patients. Follow-up examination results conducted 10 days, 3 and 6 months after treatment have shown significant improvement of clinical condition relating to pain relief, improved mobility, which was shown also on the follow-up MRI scans of the affected joints.

Speaker
Biography:

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

 

Abstract:

We describe a population of quiescent pluripotent stem cells within peripheral nerves in adult mice. These cells are induced into exuberant proliferation by either exposure to the human cytokine BMP2, a commercially vended bone
inducing agent (InfuseTM) or by physical trauma to the nerve. The sciatic nerves of adult 8 to 16 week old Balb/c mice were surgically exposed and stimulated with 60 ng of rhBMP2 or by mechanical compressive force. Both methods result in a massive proliferation of cells within the treated nerves. Harvesting nerves at 24 or 48 hours allowed us to culture them in restrictive
media. The cells fulfill many of the criteria for embryonic stem cells. Immunohistochemical staining has demonstrated that these cells express the four critical genetic markers for embryonic stem cells: Oct4, Sox2, Klf4 and c-Myc. As hoped, the
immunohistochemical staining is confined to the cell nucleus. We have also demonstrated the abundant presence of mRNA specific for these markers by Polymerase Chain Reaction (PCR) techniques. We have successfully induced differentiation of these cells into osteoblasts, endothelial cells, ectoderm and endoderm, as demonstrated by morphology, immunohistochemistry and PCR. These cells may represent an attractive potential new source of cells for regenerative therapies, as a small biopsy of a non-essential cutaneous nerve could be used to grow and differentiate in culture self-specific therapeutic cells for an individual patient, reducing or possibly eliminating risk of immune rejection, malignant transformation and teratoma formation. We suggest that they be called Nerve Derived Adult Pluripotent Stem cells or NEDAPS cells.

Janet Downie

Roslin Cell Therapies, UK

Title: Ensuring successful technology transfers for clinical manufacture

Time : 12:25-12:45

Speaker
Biography:

Janet Downie is the Chief Executive Officer for Roslin Cell Therapies, a leading cell therapy contract manufacturer and process development company based in Edinburgh. She has completed her BSc in Biological Sciences with over 20 years’ experience within the life sciences industry in Scotland with many years’ experience in cell therapy manufacturing and GMP translation. She was previously worked as Chief Operating Officer for Roslin Cells where she spent 8 years setting up and developing the cell therapy division before the Roslin Cell Therapies subsidiary was formed to enable investment and company growth. She is the Human Tissue Authority, Designated Individual and MHRA License Holder for the Roslin Cells GMP Cellular Therapy Facility within the Scottish Centre for Regenerative Medicine. She is a Member of the BIA Manufacturing Advisory Committee and the Research Quality Assurance (RQA) GMP Committee.

Abstract:

Successful technology transfers can be defined by the ability to provide well documented evidence of the routine manufacture of the therapeutic product using a reproducible manufacturing process and quality control testing regime, measurable against a pre-defined set of specifications. Key to success is the establishment of an effective overarching technology transfer framework at both the transferring and receiving sites, in addition to a full understanding of the process before transfer. In this presentation we present a practical case study on the transfer of a process for production of human embryonic stem cell lines for the manufacture of cell therapy products to treat Parkinson’s and Huntington’s disease. We will detail the steps involved in the translation of the research protocol through to a fully GMP compliant process. We will highlight the main drivers for success, including the generation of an effective communication strategy and a technology transfer protocol which covers the technical gap analysis, quality risk management, qualification of methods, facilities, equipment, analytical assays and regulatory strategy. We explore the key stages of the process and its challenges and discuss mechanisms to ensure that the transfer is successful.

Speaker
Biography:

Jane Lebkowski has been actively involved in the development of cell and gene therapies since 1986 and is currently a Chief Scientific Officer and President of R&D at Asterias Biotherapeutics Inc, where she is responsible for all preclinical and product development of Asterias’ products. From 1998 to 2012, she was a Senior Vice President of Regenerative Medicine and Chief Scientific Officer at Geron Corporation. Before joining to Geron, she was a Vice President of R&D at Applied Immune Sciences. Following acquisition of Applied Immune Sciences by Rhone Poulenc Rorer (currently Sanofi), she also served as a Vice President of Discovery Research. She has received her PhD in Biochemistry from Princeton University in 1982 and completed her Postdoctoral Fellowship at the Department of Genetics, Stanford University in 1986. She has published over 70 peer reviewed papers and has 13 issued US patents. She is on the Board of Directors of the American Society for Gene and Cell Therapy and also served as an Industry Representative to FDA’s Office of Cell, Tissue and Gene Therapy Advisory Board.

Abstract:

Human Embryonic Stem Cells (hESCs) can proliferate indefinitely yet, upon appropriate cues, differentiate into all somatic cell lineages. These two properties of hESCs enable the development of hESC-derived therapeutic cell populations which can be batch manufactured in central manufacturing facilities, cryopreserved and distributed for “on demand” use at healthcare providers. Protocols have been developed to differentiate hESCs into neural, cardiomyocyte, hepatocyte, islet, osteoblast, chondrocyte and hematopoietic cell populations which have been shown to be functional in either in vitro or in vivo animal models of human disease. Our group has established protocols to produce oligodendrocyte progenitors that upon transplantation into animals with spinal cord injuries can remyelinate denuded axons induce axonal sprouting and improve locomotor activity. Extensive preclinical studies have been completed to examine the activity, bio-distribution, dosing, delivery and potential toxicity and tumorigenicity of the http://stemcell-regenerativemedicine.conferenceseries.com/http://stemcell-regenerativemedicine.conferenceseries.com/ progenitors. The safety of these cells is now being tested in the clinic in subjects with complete spinal cord injuries. In addition our team has developed methods to produce dendritic cells from hESCs that have the antigen processing and presentation functionality to stimulate immune responses. In collaboration with Cancer Research UK, Asterias is preparing for a clinical trial using these hESC derived dendritic cells as a cancer immunotherapy in non-small cell lung carcinoma in the neoadjuvant setting Human Embryonic Stem Cells (hESCs) can proliferate indefinitely yet, upon appropriate cues, differentiate into all somatic cell lineages. These two properties of hESCs enable the development of hESC-derived therapeutic cell populations which can be batch manufactured in central manufacturing facilities, cryopreserved and distributed for “on demand” use at healthcare providers. Protocols have been developed to differentiate hESCs into neural, cardiomyocyte, hepatocyte, islet, osteoblast, chondrocyte and hematopoietic cell populations which have been shown to be functional in either in vitro or in vivo animal models of human disease. Our group has established protocols to produce oligodendrocyte progenitors that upon transplantation into animals with spinal cord injuries can remyelinate denuded axons induce axonal sprouting and improve locomotor activity. Extensive preclinical studies have been completed to examine the activity, bio-distribution, dosing, delivery and potential toxicity and tumorigenicity of the oligodendrocyte progenitors. The safety of these cells is now being tested in the clinic in subjects with complete spinal cord injuries. In addition our team has developed methods to produce dendritic cells from hESCs that have the antigen processing and presentation functionality to stimulate immune responses. In collaboration with Cancer Research UK, Asterias is preparing for a clinical trial using these hESC derived dendritic cells as a cancer immunotherapy in non-small cell lung carcinoma in the neoadjuvant setting

Biography:

Serban San-Marina has completed his undergraduate and graduate studies at the University of Toronto, Medical studies at the Carol Davila School of Medicine and holds a PhD in Biology from York University. He has completed his Post-doctoral fellowships at Penn State in T-cell Immunobiology and at the Ontario Cancer Institute in Leukemia Transcription Factor Research. In 2006, he has co-founded Biostatistix for repurposed drug discovery. He has joined the Mayo Clinic in 2013 where his interests are in small molecule-directed stem cell reprogramming for regenerative medicine.

Abstract:

In spite of extraordinary recent progress in stem cell research, the replacement of tissues of the human body is currently unachievable with existing protocols. Furthermore, the need to replace damaged tissue and organs compel the development of technologies poised for early adoption that are sufficiently flexible to accommodate a personalized/precision approach. The current innovation deficit is due in part to limited choices of starting materials, incomplete knowledge of the factors affecting lineage commitments and limitations in gene delivery systems. To enable faster ‘go/no go’ testing of new hypotheses, there is a need to increase reprogramming efficiency. We are addressing the issue or restoring organ functionality using small molecule-assisted protein reprogramming and stress-resistant pluripotent stem cells. To enable efficient reprogramming, small molecule process boosters are identified by zebrafish (zf)-assisted screening of compound libraries, including FDA-approved drugs that can be rapidly re-purposed. To illustrate the transforming potential of this technology we have selected as an end point, the regeneration of hair-like cells in the cochlea.

Speaker
Biography:

Hazem Barmada is a Cardiovascular and Thoracic Surgeon. He was graduated from St. Andrews and Manchester Universities in 1971 and 1974, respectively. He was active in martial arts in Britain from 1968 to 1984 and was a Medical Officer to the Martial Arts Commission and other major karate organizations in GB from 1974 to 1984. He is a Fellow of the Royal College of Surgeons of Edinburgh in General and Cardiothoracic Surgery, the intercollegiate British Boards in Cardiothoracic Surgery and the Royal Society of Medicine in London and is also a Member of the Society of Thoracic Surgeons and American College of Phlebology. He has two patents and published a number of papers. His interests include regenerative medicine and stem cell research, sports injuries and venous and lymphatic disease.

Abstract:

Stromal vascular fraction (SVF) was first isolated from adipose tissue around 1970, but it was not until early this century that its potential in providing regenerative cells for treatment of various medical conditions was realized. SVF has proved very effective in helping manage many hitherto difficult or untreatable conditions, including severe degenerative joint disease (DJD), medically. Nonetheless, it has not been effective in every case, especially in the more severe cases of DJD. Extracorporeal Pulse Activation Technology (EPAT), Alias Dictus Shock or Pressure Wave Therapy (ESWT), is a non-invasive technology platform of Storz Medical that employs acoustic pressure waves to affect a mechanico-transduction response at the cellular level, which leads to cell activation, improved metabolism, angiogenesis, neovascularization and improved healing. This has been used as a stand-alone modality for treating various musculoskeletal conditions in Germany over the past twenty years. In four patients with severe DJD who have either refused surgery or had undergone multiple unsuccessful surgeries, we found the addition of EPAT to the deployment of SVF intravenously and locally, highly effective in decreasing pain, reducing stiffness and increasing functionality.

Speaker
Biography:

John Yu is Distinguished Chair Professor/Director, Institute of Stem Cell/Translational Cancer Research, CGMH. He is also Distinguished Visiting Research Fellow at Institute of Cellular & Organismic Biology, Academia Sinica, and was the Director for the same Institute (2002-2009). He is the founding President for Taiwan Society for Stem Cell Research. Dr. Yu was elected to serve in many ISSCR Committees USA, the Steering Committee of Asia-Pacific Stem Cell Network, and advisor for Stem Cell Biology, Kumamoto Univ. He was Director of Exp. Hematology (1998-2002) at Scripps Research Institute, USA. He received an Established Investigatorship Award from American Heart Assoc. and many other awards.

Abstract:

All cells carry an array of sugars or glycans that have the ability to modulate or mediate cellular interactions with other cells, and regulate development and functions of an organism. Nearly all aspects of biology are affected by glycan-mediated events. Glycans also participate in multiple fundamental cellular mechanisms that contribute to health and disease, yet they pose a great challenge to study as glycans are extremely heterogeneous, stereochemically complex, and glycosylation is not under direct genetic control. Here, we employed glycomic analysis to address two important biomedical issues: switching of glycosphingolipid core structures during differentiation of human embryonic stem cells (hESCs) and development of glycan-targeted cancer vaccine cancer. First, we will describe a systematic survey of expression profiles of GSLs and glycoproteins in hESCs and their differentiated derivatives along various lineage specifications. Based on MALDI-MS and MS/MS analyses, we have found expressions of a number of unique GSLs in the undifferentiated hESCs and induced pluripotent stem (iPS) cells, and also a close association of the GSL expressions with lineage-directed differentiation. Secondly, Globo H, a known biomarker for cancers, was found to be highly expressed in undifferentiated hESCs and iPS cells but disappeared upon differentiation, making Globo H to be an ideal target for cancer immunotherapy. Our recent findings of Globo H ceramide as immune checkpoint molecules and angiogenic factors provide further impetus for Globo H-targeted immunotherapy. These studies thus suggest that biosignatures unique for hESCs and iPS cells are potential targets for development of cancer therapeutics cancer vaccines

 

Speaker
Biography:

Yechiel Elkabetz has earned his BSc, MSc and PhD in Cell Biology from Tel Aviv University. He has started his investigation of human pluripotent stem cells (PSCs) and neural stem cells (NSCs) in 2004 at Lorenz Studer group at Sloan-Kettering Institute, NY. His study at the Sloan led to the isolation of a novel early type of NSCs termed rosette neural stem cells, which became a platform for understanding early neural specification events in vitro. In 2009, he established his lab at Tel Aviv University

Abstract:

Modeling key cell fate decisions and heterogeneity during the establishment and ontogeny of cortical neural progenitors is fundamental for revealing origin of diverse lineages, identifying molecular forces regulating distinct potencies and developing strategies for generating homogeneous cortical neural stem cell (NSC) populations for regenerative medicine. Here we report our recent progress in developing such approaches and their implications. We isolated consecutive neural progenitors derived from human pluripotent stem cells (PSCs) differentiated along cortical development based on their notch activation state. We first isolated notch active CNS neuroepithelial cells exhibiting high proliferation and broad potential. These successively yield early and mid cerebral neurogenic radial glia followed by gliogenic radial glia, together recapitulating hallmarks of NSC ontogeny, cortical lamination and glial transformation in notch dependent manner. We used isolated stages as modules to identify forces driving cell fate transitions. We employed gene expression analysis and epigenetic profiling combined with computational approaches to infer key regulators progressively remodeling the epigenetic landscape and followed by shRNA functional validation. This allowed uncovering a core gene regulatory network of stably expressed transcription factors that dynamically interacts with stage specific factors to regulate cortical NSC fate transition. We further used these data to identify dynamics of pathway activation during this process and based on these we developed a streamlined and robust protocol for efficient cortical cell fate conversion from naive and primed PSCs using small molecules. We also used this method to efficiently develop cerebral organoids that are homogeneous for cortical regional fate and stem cell state. To exemplify the utility of the new protocol to model disease, we generated a microcephaly PSC line by introducing an autosomal recessive microcephaly mutation. We observed dramatic differences in microcephaly vs. WT organoids that were only apparent when specifically derived by our new protocol. We further identified abnormal cortical layer lamination and precocious differentiation in microcephaly organoids accompanied by cytoarchitectural and cellular defects, hence leading to a novel delineation of early pathology of microcephaly in cortical NSCs.

Dennis M Lox

Sports and Regenerative Medicine Centers, USA

Title: Sports medicine: Stem cells in the OA and AVN patient
Speaker
Biography:

Dennis M Lox has attended the University of Arizona where he was Phi Beta Kappa. He has received his Medical degree at the Texas Tech University Health Sciences Center and his Residency Training in Physical Medicine and Rehabilitation at the University of Texas Health Sciences Center at San Antonio. He has maintained a private practice in the Tampa Bay, Florida and presently in Beverly Hills, California. He specializes in musculoskeletal disorders, sports medicine and regenerative medicine. He has edited two medical textbooks, written eight textbook chapters and scientific publications. He has also lectured extensively in the areas of regenerative and sports medicine.

Abstract:

The use of regenerative medicine applications such as stem cell therapies may have a common thread in the management of sports medicine patients. Trauma is a precipitating event in sports for the development of early onset osteoarthritis, as well as Avascular Necrosis (AVN). An understanding of the underlying pathophysiological processes involved in both post traumatic osteoarthritis and Avascular Necrosis (AVN) may direct treatment towards the use of regenerative medicine and stem cells. The progression of post traumatic osteoarthritis and AVN after sports injuries may direct early treatment methodologies toward a regenerative model, rather than a time sensitive progressive degenerative cascade. Case representations will demonstrate a parallel tract for the investigation and management of sports medicine patients who are at risk for or developed post-traumatic osteoarthritis and those with Avascular Necrosis (AVN).

Speaker
Biography:

Zhang is an Associate Professor in the University of Texas Medical School at Houston. He received his Ph.D. from MD Anderson Cancer Center and postdoctoral training from Howard Hughes Medical Institute, Baylor College of Medicine. His research focuses on epigenetic mechanism of Na+ and water homeostasis, with a special emphasis on histone H3 K79 methyltransferase Dot1l and the epithelial Na+ channel. He created Af17 knockout and Dot1l conditional knockout mice. Recently, he began to study biomarkers and stem cells in kidney injury and repair. He has published >40 peer-reviewed papers and received funding from NIH, AHA and ASN.   

Abstract:

Connecting tubule (CNT) interconnects nephron and collecting duct (CD), which arise from kidney mesenchyme and the branching ureteric epithelium, respectively, to generate the functional tubular networks. CNT is thought as a product of reciprocal induction between the adjoining segments. The identity of the ureteric progenitors contributing to CNT remains virtually unknown. Recently, we reported that Aqp2-expressing cells with disrupted Dot1l give rise to principal cells (PC) and intercalated cells (IC). However, whether such derivation occurs naturally and whether Aqp2+ progenitors contribute to CNT has never been addressed. Here, we generate a new mouse model (RAC) in which Aqp2 lineage is genetically traced by red fluorescence protein. With high-resolution image analysis, we demonstrate that Aqp2+ progenitors naturally give rise to not only PC and IC, but also several types of CNT cells. CNT can be divided into three molecularly distinct segments. These segments contain CNT/DCT transitional cells, which originate from Aqp2+ progenitors, but gain expression of NCC, a well-established DCT marker. Our study highlights the molecular identity and the origin of novel and distinct CNT segments and discovers Aqp2+ progenitors as one of the origins of various types of cells not only in the CD but also in the CNT. Therefore, our study reports a novel mouse model that faithfully traces Aqp2 lineage and demonstrates a novel function of Aqp2+ progenitors in CNT formation. The discovery of the CNT segments and Aqp2+ progenitors may facilitate their isolation and functional evaluation

Speaker
Biography:

Naglaa Kamal Idriss has completed her PhD from Birmingham University and Postdoctoral studies from Southampton School of Medicine. She is the Member of International Society for Stem Cell Research (ISSCR) and European Society of Cardiology, ESC working group on Coronary pathophysiology and microcirculation. She has published more than 15 papers in reputed journals.

Abstract:

Background: Human umbilical cord blood (UCB) cells and rat bone marrow mesenchymal stem cells (BM-MSCs) have many advantages as grafts for cell transplantation.

 

Aim: The aim of this study was to evaluate the treatment effects of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) on rat liver fibrosis induced by carbon tetrachloride. Intrasplenic and intravenous transplantations were examined to evaluate the effects of different injection routes on the liver fibrosis model at 12 weeks after transplantation.

 

Methods & Results: Experimental animals include 24 male white albino rats were 4 weeks old, weighing between 130 and 150 g. Liver fibrosis was induced by subcutaneous injection of carbon tetrachloride (CCl4) at a dose of 0.2 ml/100 g body weight of 40 ml/L CCl4 dissolved in equal volume of castor oil. The injection was given twice weekly for 6 week rats were divided into the following groups: G1 (Control group): 6 rats received 0.2 ml/100 g body weight of castor oil twice weekly for 6 weeks. G2 (CCl4 group): 6 rats received 0.2 ml/100 g body weight of CCl4. Liver fibrosis was determined by histopathological examination. G3 (CCl4/BM-MSCs group): 6 rats received CCl4 as previous. The rats were infused with 107 BM-MSCs/rat intravenously (through tail vain) and scarified after 3 months. G4 (CCl4/BM-MSCs group): 10 rats received CCl4 as previous and followed by injection of 107 BM-MSCs intrasplenic and scarified after 3 months. At 4, 8 and 12 weeks from stopping CCl4 and administration of stem cells, venous blood was collected from the retro-orbital vein to assess serum albumin and alanine transaminase (ALT). All rats were sacrificed with CO2narcosis and the liver tissue was harvested for histopathological examination and real time PCR analysis. Isolation and Culture of BM-MSCs. Cultured MSCs were confirmed by morphology, labeling Stem Cells with GFP. Serum ALT and albumin were assessed using colorimeter kits according to manufacture instructions.Histopathological examination liver tissues were collected and divided into two sections. The first section was assessed for tracing of injected labeled cells with GFP. The second section was washed with PBS and fixed overnight in 40 g/L paraformaldehyde at 4 °C for evaluation of fibrosis. Real Time PCR (qRT-PCR) for Quantitative Expression of IL-6, IL1-β, CK18, INF-γ and HGF. Western blotting for human SIRT-1: The results of the blots are presented as direct comparisons of the area of the apparent bands in autoradiographs and quantified by densitometry using the Bio- Rad Image software. ELISA: Connective tissue growth factor(pg/ml) was assessed.

 

Conclusion: Notably, there were no differences in treatment effects between intravenous and intrasplenic administrations. The IV injection group had significantly different (p<0.05) serum connective tissue growth factor levels compared with the intrasplenic injection group. However, liver serum markers and liver histology classification of both groups showed no differences (p>0.05). Considering safety, BM-MSC transfusion via a peripheral vein is a potential method for liver fibrosis treatment. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment.

 

Speaker
Biography:

SuEllen Pommier is an Associate Professor in the Department of Surgery, Division of Surgical Oncology at Oregon Health & Sciences University, Portland, Oregon, USA. Her area of expertise is in the area of Breast Cancer. Her direction of focus is that of a geneticist, in that she strives to identity and characterize the signaling profiles of mutations that are present in breast cancer stem cells.

 

Abstract:

Background: Responses to neo adjuvant chemotherapy (NAC) are used as surrogates to evaluate systemic response in patients. 85% of patients have residual disease (RD) implying some degree of treatment resistance. We hypothesize that the frequencies and mutation status of breast cancer stem cells (BCSC) in the tumor will correlate with having RD after NAC.

Methods: Fresh surgical specimens collected from invasive ductal carcinomas (IDC) before and after NAC. BCSC were counted and mutations identified by array platform, assessing 2800 mutations in 50 tumor suppressor and oncogenes. Changes in tumor size, receptor status, BCSC frequencies and mutation identification were compared between treatment naïve IDC and IDC after NAC.
Results: There were 39 women with IDC, of which 15 received NAC. 
Treatment naive and NAC treatment groups had similar clinical characteristics except for an increase of ER-/PR- tumors in the latter (8% vs. 40%, p=0.04). Mean sizes of naïve tumors were 3.0 cm and those receiving NAC were 2.6 cm. Mean size of RD was 3.4 cm. The frequencies of PIK and TP53 oncogene mutations were 32% and 3.6%, respectively, in treatment naive tumors compared to 36.4 % and 36.4%  in RD (p=0.016). Specific BCSCs harboring these mutations had a 3.7 fold higher frequency in RD among both ER/PR positive and negative tumors (p<0.0004). 
Conclusions: Following NAC, breast cancer RD contained higher frequencies of BCSCs carrying aggressive cancer mutations compared to tumors prior to NAC or tumors with no RD. These cell populations are not only resistant but may be increased by NAC. RD molecular assessment provides opportunities to evaluate the mechanisms of response/resistance to NAC, as well as to direct further therapies. 

Speaker
Biography:

Huanhuan Joyce Chen has received her PhD degree in Biomedical Engineering at Cornell University. She is currently a Postdoctoral Associate with Dr. Harold Varmus at Weill Cornell Medicine. She has published more than 15 papers in reputed journals such as Nature Biotech and Cell Stem Cell and received awards including National Science Foundation Graduate Research Fellowship and National Cancer Institute Physical Sciences in Oncology Young Investigator Award.

Abstract:

Current cancer research hinges on developing models that accurately recapitulate cancer disease phenotypes. Though animal models are very useful tools, the major limitation stems from species variation that animal models can be considerable different to human cancers and fail to faithfully recapitulate human conditions. To address this issue, we engineered an ex vivo colon cancer models by recellularization of human native matrix with human colonic stem cells derived cell resources. We followed to demonstrate the significance of the organotypic human-originated model in studying cancer biology by combining transposon-based mutagenesis. Another problem rises from the availability of tissue-specific cell types representative of clinical disease features, especially in the lung cancer types with the scarcity of primary tumors for generation of cell lines. Here, I will also describe my current efforts to synthesize cellular engineering, single-cell methods with human pluripotent stem cell technology for lung cancer modeling.

Speaker
Biography:

Mohammad Ghasemzadeh-Hasankolaei has graduated in Veterinary Medicine in 2005 and joined PhD program in Veterinary Reproductive Sciences in 2006; simultaneously, he started his studies on stem cells at Royan Institute, Iran. He has published a number of papers in the field of stem cells and germ cells. He is working as an Assistant Professor at Babol University of Medical Sciences, Iran since 3 years. He has founded the “Stem Cells Research Lab.” in the “Infertility and Reproductive Health Research Center” of the university in 2013.

Abstract:

Here we describe our three different research experiences in the field of generation of male germ cells (GCs) from mesenchymal stem cells (MSCs). In the first research, ram bone marrow (BM)-MSCs, were induced to differentiate into male GCs by different methods; treatment with different concentrations of retinoic acid (RA) for 14 and 21 days, 100 ng/ml BMP4 and BMP8b and also 10 ng/ml TGFb1, all for 21 days (all in separate groups). Results showed that, the most efficient methods were 21 days treatment with 10 µM RA and 10 ng/ml TGFb1. Transplantation of the induced GCs into testes revealed that, after 2 months, although, a number of cells could home in the seminiferous tubules, they could not differentiate farther from spermatogonia state. In the second study, we evaluated the potency of intact autologous rat BM-MSCs for regeneration of testis germinal epithelium after induction of infertility with busulfan injection. Evaluations after 4, 6 and 8 weeks showed that a number of BM-MSCs was located in the germinal epithelium and expressed spermatogonia specific markers. In our third study, we treated mouse amniotic membrane MSCs with 50 ng/ml BMP4 for 5 days and immediately with 10 µM RA for 12 days. Eventually, there were some germ-like cells in the culture. Finally, although, in all of our experiments, a number of treated cells differentiated into the GCs, the efficiency was very poor. It seems it is still too soon to have developed functional GCs from MSCs in vitro.

Speaker
Biography:

Prof. Jun HU completed his MD from Xiangya Medical College of Zhongnan University and postdoctoral studies from South China Normal University. He is the director of the department of orthopaedics, in Shantou University Medical College. His research team is interested in the development of innovative approaches for enhancing bone fracture healing and cartilage repair. He has published a number of original papers in reputed journals, including Nanomedicine, the Journal of Biological Chemistry, Scientific Reports, and Journal of Biomedical Optics. He also serves as a nominated reviewer for NSFC proposals in China. 

Abstract:

Extracorporeal shockwave (ESW) has been shown of great potential in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but it is unknown whether this osteogenic promotion effect can also be achieved in other MSCs (i.e., tendon-derived stem cells (TDSCs) and adipose-derived stem cells (ADSCs)). In the current study, we aimed not only to compare the osteogenic effects of BMSCs induced by ESW to those of TDSCs and ADSCs; but also to investigate the underlying mechanisms. We show here that ESW (0.16 mj/mm2) significantly promoted the osteogenic differentiation in all the tested types of MSCs, accompanied with the downregulation of miR-138, but the activation of FAK, ERK1/2, and RUNX2. The enhancement of osteogenesis in these MSCs was consistently abolished when the cells were pretreated with one of the following conditions: overexpression of miR-138, FAK knockdown using specific siRNA, and U0126, implying that all of these elements are indispensable for mediating the effect of ESW. In addition, our study provides converging genetic and molecular evidence that the miR-138-FAK-ERK1/2-RUNX2 machinery can be generally activated in ESW-preconditioned MSCs. More importantly, this machinery has also been confirmed by our in vivo experiments, including nude mice spontaneous implantation model and rat femur close fracture model. All these findings suggest that ESW may be a promising therapeutic strategy for the enhancement of osteogenesis of MSCs, regardless of their origins.