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.

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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. 

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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.

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.

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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.

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.

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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.

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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. 

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.

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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.   

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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 (R^AC) 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

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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.

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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).

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

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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.

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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.

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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.

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.

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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.

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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.

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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

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