Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 8th World Congress and Expo on Cell & Stem Cell Research Orlando, Florida, USA.

Day 1 :

Keynote Forum

Haval Shirwan

University of Louisville, USA

Keynote: Targeted deletion of pathogenic T effector cells as a robust means of allograft tolerance

Time : 10:00-10:30

OMICS International Stem Cell Research 2017 International Conference Keynote Speaker Haval Shirwan photo
Biography:

Haval Shirwan is Dr. Michael and Joan Hamilton Endowed Chair in Autoimmune Disease, Professor of Microbiology and Immunology, Director of Molecular Immunomodulation Program at the Institute for Cellular Therapeutics. He conducted his Graduate studies at the University of California in Santa Barbara, CA, and Postdoctoral studies at California Institute of Technology in Pasadena, CA. He joined the University of Louisville in 1998 after holding academic appointments at various academic institutions in the United States. His research focuses on the modulation of immune system for the treatment of immune-based diseases with particular focus on type 1 diabetes, transplantation, and development of prophylactic and therapeutic vaccines against cancer and infectious diseases.  He is an inventor on over a dozen of worldwide patents, founder and CEO/CSO of FasCure Therapeutics, LLC, widely published, organized and lectured at numerous national/international conferences, served on study sections for various federal and non-profit funding agencies, and is on the Editorial Board of a number of scientific journals. He is member of several national and international societies and recipient of various awards.

Abstract:

Transplantation of pancreatic islets as a source of beta cells producing insulin has proven effective in improving metabolic control/quality of life and preventing severe hypoglycemic events in patients with type 1 diabetes. Rejection of islets mediated by T cells is a major limitation of clinical islet transplantation, which is presently controlled by standard immunosuppression.  Chronic use of immunosuppression is not only ineffective in controlling rejection, but also has various side effects compromising the life quality of graft recipients. Therefore, there is an acute need for the development of targeted immunomodulatory approaches that have efficacy and safety features.  Inasmuch as T effector cells are the major culprit of allograft rejection and their pathogenic function is controlled by T regulatory cells, we have recently developed novel forms of immune ligands to target pathogenic T cells for physical elimination, while simultaneously expanding protective T regulatory cells.  The application of this concept to pancreatic islet grafts for the treatment of diabetes will be discussed.

Keynote Forum

Mahendra S.Rao

Q Therapeutics, Inc., USA

Keynote: IPSC derived MSC and MSC engineering

Time : 10:30-11:00

OMICS International Stem Cell Research 2017 International Conference Keynote Speaker Mahendra S.Rao photo
Biography:

Dr. Mahendra S. Rao, M.D., Ph.D., serves as the Vice President of Strategic Affairs at Q Therapeutics and the Vice President of Regenerative Medicine at the New York Stem Cell Foundation. Dr. Rao is a Scientific Co-Founder of Q Therapeutics, Inc. He has been Chairman of Scientific & Medical Advisory Board and Chief Clinical & Regulatory Advisor at CBR Systems, Inc. since February 2015. Dr. Rao serves as Chairman of the Scientific Advisory Board and Chief Strategy Officer at Q Therapeutics, Inc. Dr. Rao was a Scientific Co-Founder and Chief Scientific Consultant of Q Therapeutics, Inc. He heads stem cell research and development program at Invitrogen Corp. He is an expert in glial stem cell biology and for the last 20 years has acted as a Scientific Consultant for a broad range of constituencies in academia, government, regulatory affairs and industry. He is involved in stem cell research for more than a decade. Dr. Rao served as the Chief of the Laboratory of Stem Cell Biology at the NIH. Before joining the NIH, Dr. Rao led the Stem Cell and Regenerative Medicine division at Life Technologies. He serves as a Member of Scientific Advisory Board for IPSC Banking and CGMP Production at Allele Biotechnology and Pharmaceuticals, Inc. He serves as Member of the Scientific Advisory Board at ReNeuron Group plc. He has been an Independent Director of Cesca Therapeutics Inc. since April 1, 2014. Dr. Rao has served as the Chairman of the FDA's Cell and Gene Therapy Advisory Committee. He served as chair of the FDA's Center for Biologics Evaluation and Research (CBER) Advisory committee. Dr. Rao serves as Vice President for Regenerative Medicine at The New York Stem Cell Foundation Research Institute. 

Abstract:

Mesenchymal stem cells have been approved for therapy in multiple geographies and for multiple indications. However, manufacturing from an adult source has been a challenge for allogeneic use. We have proposed that MSC derived from IPSC may solve this sourcing issue and offer several advantages such as the ability to prospectively identify the right allelic phenotype and the possibility of genetically modifying the cells to enhance their utility.

OMICS International Stem Cell Research 2017 International Conference Keynote Speaker Paul J Davis photo
Biography:

  • Dr Paul J Davis is a graduate of Harvard Medical School and had his postgraduate medical training at Albert Einstein College of Medicine and the NIH. His academic positions have included Chair, Department of Medicine at Albany Medical College. He has served as President of American Thyroid Association, as a member of the Board of Directors of the American Board of Internal Medicine and he is Co-Head, Faculty of 1000 – Endocrinology. He serves on multiple Editorial Boards of His scientific interests include molecular mechanisms of actions of nonpeptide hormones, particularly, thyroid hormone. He and his colleagues described the cell surface receptor for thyroid hormone on integrin αvß3 that underlies the pro-angiogenic activity of the hormone and the proliferative action of the hormone on cancer cells. He has co-authored more than 200 original research articles and 30 textbook chapters and he has edited three medical textbooks.

Abstract:

Clinical evidence in a limited number of patients supports the concept that glioblastoma multiforme (GBM) is a thyroid hormone-dependent cancer. In vitro evidence indicates that L-thyroxine (T4), the principal secretory product of the thyroid gland, at physiological concentrations stimulates proliferation of glioma/GBM cancer cells via a polyfunctional cell surface receptor for T4 on the extracellular domain of cancer cell plasma membrane integrin avb3. This action of T4 is blocked by nanoparticulate tetraiodothyroacetic acid (Nanotetrac, Nano-diamino-tetrac, NDAT). Tetrac in this NDAT formulation is covalently bound via a diaminopropane linker to a poly(lactic-co-glycolic acid) (PLGA) nanoparticle. We have examined histopathologically the induction by NDAT of devascularization, of necrosis and apoptosis in U87MG human GBM cell xenografts in nude mice. Treatment regimen was 1 mg tetrac equivalent/kg body weight s.c. as NDAT daily X10 d, begun 2 d following tumor cell implantation when tumor volume estimates were 350 mm3. Xenografted control animals received void nanoparticulate PLGA.  Xenograft weight in treated animals at sacrifice was reduced by 50% (P<0.01). Tumor area measured in histologic sections was reduced by 80% in treated animals compared to controls (P<0.001). Blinded analysis of changes in histologic slides from xenografts revealed essentially complete loss of tumor blood vessels with NDAT (P<0.001 vs. control xenografts). This finding was associated with no evidence of hemorrhage. Eighty percent of the cell population in grafts was either necrotic or apoptotic (P<0.001 vs. control) and cell density was reduced by 60% vs. control tumors (P <0.001 vs. control). Mitotic figures/field examined was reduced by 80%.  In summary, NDAT, acting at the thyroid hormone-tetrac receptor on the extracellular domain of integrin avb3, devascularized human GBM xenografts with resultant widespread necrosis.  In the tumor cell population that was not necrotic, drug-induced apoptosis was documented. The thyroid hormone receptor on avb3 in U87MG cells is a single endocrine target with multiple downstream functions that are exploited by anticancer and anti-angiogenic actions of NDAT. 

Keynote Forum

Bakhos A Tannous

Harvard Medical School, USA

Keynote: Glioblastoma cells and stem cells: Imaging and gene/drug/cell therapy

Time : 11:50-12:20

OMICS International Stem Cell Research 2017 International Conference Keynote Speaker Bakhos A Tannous photo
Biography:

Bakhos A Tannous is an Associate Professor of Neurology at Harvard Medical School and Director for the Interdepartmental Neuroscience Center at the Massachusetts General Hospital. He is a member of the Dana Farber/Harvard Cancer Center and also acts as Co-Director of the Molecular Neurogenetics Unit-East. His research interest includes novel imaging, high throughput discovery of gene/cell/drug therapies for brain tumors, with a primary focus on glioma stem cells, as well as detection of tumor-specific biomarkers in blood. He has published >90 papers and serves as an Editorial Board Member of several journals.

Abstract:

Glioblastomas (GBMs) comprises >50% of all primary brain tumors and are the most malignant type with a 5-year survival rate of only 3.3%, despite standard-of-care (surgery, radiation and temozolomide). Recently it has been shown that the glioma stem-like cells (GSCs; or tumor initiating cells) sub-population of the tumor are largely responsive for tumor resistance, recurrence and patient death, thus providing a clinically-relevant model to study GBM. GBMs are highly heterogeneous and there is a complex interaction among different subtypes of tumor cells and stromal cells associated with the tumor which can modify the tumor itself as well as its microenvironment to promote tumor growth, invasion, angiogenesis and immune suppression. The transcriptome profiles of GBMs has identified four major subtypes, two of which, proneural (PN) and mesenchymal (MES), predominate with multiple subtypes residing in the same tumor. GBM with enriched MES properties typically display a more aggressive phenotype both in vitro and in vivo with pronounced radio/chemo resistance. Our goal is to understand GBM progression and therapeutic resistance to help us develop novel diagnostics/therapeutics aiming at eradicating this cancer type. Over the last several years, we have developed novel efficient gene/drug/cell therapeutic strategies that bypass the blood-brain barrier to target and eradicate patient-derived GBM stem cells model.

  • Stem Cells | Stem Cell Therapy | Stem Cell Biomarkers | Cellular Therapies | Stem Cells and Cancer | Cell and Organ Regeneration | Cell Differentiation and Disease Modeling | Stem Cell Plasticity and Reprogramming | Tumor Cell Science
Location: Orlando
Speaker

Chair

Paul J Davis

Albany Medical College, USA

Speaker

Co-Chair

Haval Shirwan

University of Louisville, USA

Session Introduction

Brian Mehling

Blue Horizon International LLC, USA

Title: Analysis of outcomes following mesenchymal stem cell therapy in subjects with musculoskeletal conditions

Time : 12:20-12:40

Speaker
Biography:

Brian M Mehling, MD, MS is a practicing American Orthopedic Trauma Surgeon, Researcher and Philanthropist. He 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. Completing his degree of Medicine at Wright State University School of Medicine, he received post graduate education through residencies and fellowships at St. Joseph’s Hospital in Paterson, NJ and the Graduate Hospital in Philadelphia, PA, while pursuing a PhD in Chemistry. He operates his own practice, Mehling Orthopedics, in both West Islip, NY and Hackensack, NJ.

Abstract:

Musculoskeletal conditions are major public health problems and often associated with reduced function and pain. Musculoskeletal related pain is affecting more than one third of the adult population worldwide. Pain reduction is one of the main outcomes to determine the success of therapy of subjects with most common orthopedic conditions. Inflammation plays an important role in the occurrence of acute and chronic musculoskeletal-related pain. Numerous investigations suggest that Mesenchymal Stem Cells (MSCs) represent a valuable tool for therapy of inflammation and regeneration of tissue damage. BHI Therapeutic Sciences offers a novel method of arthritis therapy using a patient’s own stromal vascular fraction (SVF) cells including MSCs. The therapy is available at Malacky Hospital in Slovakia. Blue Horizon International Slovakia is licensed by the Ministry of Health of Slovak Republic to provide adipose stem cell therapies for orthopedic joint applications - knees, hips, shoulders, and ankles. Procedures utilize cuttingedge technology and adult stem cells only. 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 therapy 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:

Margarita Glazova has received her PhD in 1997 from Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Science. She has performed her Post-doctoral studies at Turku Centre for Biotechnology, University of Turku/Åbo Akademi, Finland and then at East Carolina University Brody School of Medicine, Department of Physiology, Greenville NC, USA. Currently, she is Head of Lab at the Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia. Her main interests concern the study of adult neurogenesis and neural stem cells differentiation at normal and under neuropathology disease, such as epilepsy. She has published more than 30 articles in peer-reviewed scientific journals

Abstract:

The hippocampal formation is one of the most affected areas, where epileptogenesis is usually associated with dramatic pathological changes in morphology and functions. It is known that epilepsy progression is tightly connected with aberrant neurogenesis in the hippocampus. Animal models of audiogenic epilepsy are useful tools to understand the mechanisms underlying human reflex epilepsies. In our work, we have analysed hippocampal neurogenesis in Krushinsky-Molodkina rats genetically prone to audiogenic seizure (AGS). Our data demonstrated that several AGS stimulated proliferation of neural stem cells. On the other hand, audiogenic kindling led to elimination of the proliferated cells in the hippocampus. Moreover, AGS was accompanied with changing in activity of MAPK cascade, glutamate neurotransmission and expression of exocytosis proteins

 

Speaker
Biography:

Mei Wan is an Associate Professor of the Center for Musculoskeletal Research, Department of Orthopedic Surgery at Johns Hopkins University School of Medicine. She has obtained her PhD in Pathophysiology at Hebei Medical University in 1997. Her research for the past 18 years focuses on characterizing the mechanisms by which bone marrow mesenchymal stem cells (MSCs) are regulated in various physiological and pathological conditions such as bone remodeling, cancer development, vascular disorders and tissue repair/remodeling. In recent years, she found that active TGFβ can be released from tissue in response to perturbations to the local environment such as bone remodeling (Nat. Med. 2009, Cell Stem Cell 2011), arterial injury (Stem Cells 2012, Stem Cell Dev. 2014, Nature Communications 2016) and lung injury (J. Immunol. 2014, J. Immunol. 2016). The released active TGFβ stimulates the migration of MSCs to participate in tissue repair or remodeling. Currently, she is an Editorial Board Member for Journal of Bone and Mineral Research and Bone Research.

Abstract:

Recent studies suggest that a sub-population of MSCs, specifically cells expressing nestin, mobilize from their original niches to the vascular remodeling sites after arterial injury in mice. In the present study, we delineated a molecular mechanism by which the lineage commitment/differentiation of nestin+ MSCs is controlled during vascular repair. Using a genetic nestin+ cell lineage mapping mouse model, we found that nestin+ cells recruited to the injured arteries is a contributor to neointimal formation. Nestin+cells recruited to the remodeling sites represent a mixed population, with MSCs as a predominant component. More importantly, we revealed that TGFβ-activated RhoA/ROCK signaling functions as a molecular switch regarding the fate of MSCs in arterial repair/ remodeling after injury. MSCs differentiate into myofibroblasts when RhoA/ROCK is turned on, endothelial cells when turned off. The former is pathophysiologic resulting in intimal hyperplasia, whereas the latter is physiological leading to endothelial repair. Further analysis revealed that MSC RhoA activation promotes formation of an extracellular matrix (ECM) complex consisting of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF). Inactivation of RhoA/ROCK in MSCs induces matrix metalloproteinase-3-mediated CTGF cleavage, resulting in VEGF release and MSC endothelial differentiation. Our findings uncover a novel mechanism by which cell-ECM interactions determine stem cell lineage specificity and offer additional molecular targets to manipulate MSC-involved tissue repair/regeneration.
 

 

Speaker
Biography:

Abstract:

As innovators move closer to clinical success, a gap in the ability to cost effectively manufacture cell therapies has been identified. To address this gap, we have demonstrated the use of single-use expansion and harvest systems that robustly expand and recover a variety of stem cells. An additional contributor to the system is the inclusion of high quality reagents that are animal origin free, lead to better yields and are supplied with a strong regulatory dossier. We will present data regarding ease of use, yield, viability and characterization for full solution expansion and harvest of manufactured cell therapies. Start to finish solutions for expansion and harvest are key enabling technologies for success in commercializing cell therapies.

Speaker
Biography:

Vincent S Gallicchio received his PhD in Hematology from New York University and his Diploma in Medicine from the University of Arad, Romania. He performed Postdoctoral studies at the University of Connecticut Medical Center and conducted his fellowship in Hematology from the Memorial Sloan Kettering Cancer Center. He has published more than 150 research articles in peer-reviewed journals on topics focused on stem cells and hematology, seven books, many book chapters, and has been awarded eleven United States and one international patent for developmental therapeutics for AIDS and Cancer. He currently serves as a Director of Stem Cell Therapy for out-patient clinical use.

Abstract:

The science driving the current revolution in regenerative medicine continues to focus on advances in research made in tissue biology and engineering along with molecular medicine. The goal is to advance the field such that the application of stem cells can improve clinical outcomes when it addresses the issue of altered or damaged cells, tissues or body organs. Another exciting area
of research in regenerative medicine addresses the need to grow new body organs to replace damaged or dysfunction body parts, thus addressing the current problem, where there is a shortage of organs available from potential donors. If the source of stem cells is derived from the same individual in whom the body tissue or organ needs to be replaced will eliminate the problem of organ transplant rejection. Another area of research will also focus on the expanding sources of stem cells such as the use of induced pluripotential stem cells (iPCs), mesenchymal stem cells (MSC) derived from adipose and aminotic tissue or cord blood beyond blood and bone marrow. Any advance in applied use of stem cells beyond blood and immunological use is limited by the fact that cord cells are hematopoietic stem cells (which can differentiate only into blood cells), and are not pluripotential stem cells, as embryonic stem cells, which can differentiate into any type of tissue, they can be induced to “dedifferentiate” as iPCs. Cord blood has been studied as a treatment for diabetes. However, apart from blood disorders, the use of cord blood for other diseases is not a routine clinical modality and remains a major challenge for the stem cell community. Along with adipose and amniotic tissue, cord blood, chord lining, and Wharton’s jelly, have been explored as sources of MSC in order to treat conditions mediated as a function of aging and inflammation. MSC have been studied in vitro, in animal models, and in early stage clinical trials for cardiovascular diseases, as well as in osteoarthritic conditions, neurological deficits, liver diseases, immune system diseases, diabetes, lung injury, kidney injury and leukemia. This presentation will review the use of MSCs in these clinical indications.

Speaker
Biography:

Meenakshi A Chellaiah is a Tenured Full Professor at the University of Maryland School Of Dentistry, Baltimore, since 2014. Formerly, she was a tenure-track Assistant Professor (2000-2007) and tenured Associate Professor (2008-2013) at the same Institution. She has obtained her PhD from Madurai Kamaraj University,
India and completed her Post-doctoral studies at St. Louis University and Washington University, St. Louis, USA. She has published more than 60 papers in peer reviewed journals and gave oral presentations at over 100 national and international conferences.

Abstract:

Advanced prostate cancer (PCa) is androgen-independent. Studies revealed that tumor–initiating cells negative for androgen receptor (AR-) and p63, express the markers for cancer stem cells (CSCs). Recent studies indicate the involvement of stem cell markers (CD44, α2β1, CD133, NANOG, SOX2 and OCT4) in the maintenance of CSCs and relapse of the disease. A unique prostate stem cell biomarker has not yet been found. Our goal here is to characterize PCa cell lines derived from different metastases and tissue microarray (TMA) sections for CSC markers. We used PCa cell lines derived from lymph node (LNCaP), brain (DU145) and bone (PC3) metastases along with control cell lines (HPR1 and BPH1). Loss of AR activates CD44 expression in PC3 and DU145 cells. CD44 expression is negligible in AR positive (AR+) LNCaP cells. Only a sub population (<5%) of PC3 cells were CD44+/ CD133+. Of all the cell lines tested, the combined expression of CD44 and CD133 was greater in PC3 than DU145 cells. CD133+ PC3 cells were enriched by sequential antibody selection using DYNA beads. As compared with PC3 cells, CD44+/CD133+ enriched PC3 cells are integrin α2β1(+), Integrin αvβ3(-) and highly migratory in nature. Immunohistochemistry analyses of TMA sections demonstrated the expression of CD133 in a few island of cells (~1-2%) within the lumen filled with tumor cells (Stage III and IV) and in basal luminal cells. When comparing the expression levels of other stemness factor such as NANOG, SOX2 and OCT4 in PCa cells indicated above, only SOX2 expression was considerably higher at mRNA level which corresponds with an increased protein levels in PC3 cells. Knockdown of SOX2 not only reduces in vitro migration but also the expression of EMT regulatory proteins (Slug and Snail) in PC3 cells. Existence of sub-populations of CSCs [CD133+, CD44+, and integrin α2β1(+)] in bone metastatic PC3 cells and in the malignant prostatic tissue (CD44+, CD133+) suggest that they may cause PCa relapse and failure of many treatment practices. Furthermore, expression of SOX2 and CD133 in PC3 cells appears unique. These proteins may be involved in the maintenance of CSCs in bone microenvironment and could be used as a prognostic marker to detect bone metastatic spread. Further elucidation of the SOX2 target genes and inhibition of the function of SOX2 and its target gene may be useful in the manipulation of cancer progression in/at-risk of men.

Biography:

Željka Večerić-Haler works as a Medical Doctor, specialist of Nephrology at Nephrology department, University Medical Centre, Ljubljana. As a Nephrologist, she is faced with numerous challenges from the field of Nephrology on daily basis and is specially oriented in the fields of kidney transplantation, regenerative medicine and substitutive therapies of acute and end stage kidney failure. She has completed her PhD from University of Ljubljana Faculty of Medicine in 2016 and her thesis is revealing impact of immunological environment on the behavior and functions of transplanted stem cells. Her interests of research involve studies on stem cell transplantation for regeneration of kidney injury and immune tolerance in kidney transplantation.

Abstract:

In the last decade much effort has been introduced into treating toxic acute kidney injury with novel mesenchymal stem cell (MSC) approaches. Inflammation is known to play a crucial role in cisplatin induced acute kidney injury, were the inflammatory pathways were shown to be predominantly driven by T lymphocytes. However, most preclinical studies of stem cell xenotransplantation are performed on severe complex immunodeficiency animals lacking innate and adaptive immunity responses, therfore markedly
altering the real inflammatory state of the diseased and influencing natural course of illness. MSC were shown to have a great therapeutic potential in many disorders, where, it is not known whether those are equally effective in immunocompetent and immunocompromised microenvironment. Antithymocyte immunoglobulin is a polyclonal antibody preparation with multiple effects on immune system with preferential influence on peripheral T cell depletion. This drug enables dose dependant immunosupression, therefore allowing verification of the hypothesis that therapeutic functions and immunoregulatory properties of MSC are largerly affected by immunologic microenvironment and contribute to regeneration of kidney injury predominantly, when introduced in the non-inflammatory niche.

Biography:

Abstract:

The loss and degradation of articular cartilage tissue matrix play central roles in the process of osteoarthritis (OA). New models for evaluating cartilage repair/regeneration are thus of great value for transferring various culture systems into clinically relevant situations. The repair process can be better monitored in ex vivo systems than in in vitro cell cultures. I have therefore established an ex vivo defect model prepared from bovine femoral condyles for evaluating cartilage repair by the implantation of cells cultured in various ways, e.g., monolayer-cultured cells or suspension or pellet cultures of articular bovine chondrocytes representing different cell compactions with variable densities of chondrocytes. I report that the integrin subunit α10 was significantly upregulated in suspension-cultured bovine chondrocytes at passage P2 compared with monolayer-cultured cells at P1 (p=0.0083) and P2 (p<0.05). Suspension-cultured cells did not promote cartilage repair when compared with implanted monolayer-cultured chondrocytes and pellets: 24.0±0.66% for suspension cells, 46.4±2.9% for monolayer cells and 127.64±0.90% for pellets (p<0.0001) of the original defect volume (percentage of defect). Additional cultivation with chondrogenesis-promoting growth factors TGF-β1 and BMP-2 revealed an enhancing effect on cartilage repair in all settings. The advantage and innovation of this system over in vitro differentiation (e.g. micromass, pellet) assays is the possibility of examining and evaluating cartilage regeneration in an environment in which implanted cells are embedded within native surrounding tissue at the defect site. Such ex vivo explants might serve as a better model system to mimic clinical situations.

Speaker
Biography:

Chrishan S Samuel is an Associate Professor and has completed his PhD from University of Melbourne, Victoria, Australia. He has completed his Post-doctoral studies at the Stanford University School of Medicine and Molecular Medicine Research Institute. He is currently a Senior Research Fellow of the National Health & Medical Research Council of Australia and Head of the Fibrosis Laboratory at the Department of Pharmacology, Monash University (Melbourne, Victoria, Australia). He has over 125 career publications, which have been cited over 5100 times and his research interests are focused on establishing novel therapeutic strategies for organ fibrosis.

Abstract:

While stem cell-based therapies have demonstrated immunomodulatory, anti-inflammatory and tissue-reparative functions in acute disease settings, they are less effective when administered to chronically damaged organs. This is likely attributed to tissue fibrosis which can impair stem cell survival, proliferation, migration and integration with resident tissue cells. Hence, the therapeutic efficacy of human bone marrow-derived mesenchymal stem cells (MSCs) or human amnion epithelial stem cells (AECs) were evaluated in the setting of chronic allergic airways disease (AAD), in the absence or presence of an anti-fibrotic drug (serelaxin; RLX). Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA)-induced chronic AAD, were either vehicle-treated (OVA alone) or treated with MSCs or AECs alone (intranasally (i.n)-administered with 1x106 cells once weekly), RLX alone (i.nadministereddaily) or a combination of MSCs or AECs and RLX from weeks 9-11 (n=6/group). Measures of airway inflammation (AI), airway remodeling (AWR) and airway hyper-responsiveness (AHR) were then assessed. OVA-injured mice exhibited exacerbated AI, epithelial damage/thickness, sub-epithelial and total collagen deposition (fibrosis) and AHR compared to their saline-treated counterparts (all p<0.01 vs. saline-treated controls). RLX or AECs (but not MSCs) alone normalized epithelial thickness and partially diminished the OVA-induced fibrosis and AHR by ~40-50% (all p<0.05 vs. OVA alone). Furthermore, the combination treatments normalized airway epithelial thickness, fibrosis and AHR to that in normal mice and significantly decreased AI. These findings showed that the presence of an anti-fibrotic enhanced MSC- or AEC-induced reversal of the three central components of chronic AAD/asthma, to a greater extent than stem cell-treatment alone.

Speaker
Biography:

Helen McGettrick completed her PhD in 2006 and followed 3 Post-doctoral research positions at University of Birmingham (UK). She was appointed as a University Fellow in Inflammation Biology in 2011, and a year later, she successfully won a five year Arthritis Research UK Career Development Fellowship. She was recently awarded the prestigious “Garrod Prize” by the British Society for Rheumatology in 2016. She is an Honorary Lecturer at the University of Glasgow and Newcastle University (UK). She has more than 30 published articles with ≈ 760 citations, has filed 3 patents and received funding from Welcome Trust, Pfizer and British Heart Foundation.

Abstract:

Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage-induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC from bone marrow or adipose tissue- on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα-treated EC, but MSC-derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL-6 and TGFβ1 signaling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them and mature adipocytes from adipose tissue were all immuno-protective. Thus disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive 'abnormal' adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immuno-protective phenotype.

Speaker
Biography:

Yael Porat has obtained PhD in Immunology from Sackler School of Medicine and is the Founder and CEO of BioGenCell, a Biotechnology Company focusing on Stem Cell Therapy and Regenerative Medicine. She previously served as Head of Global Biological Development at Teva Pharmaceuticals and CTO at TheraVitae, where she led research on therapies for patients with cardiovascular diseases.

Abstract:

Background: Vascular diseases including cardiovascular and peripheral vascular are a major cause of morbidity and mortality worldwide. Critical Limb Ischemia (CLI), the most serious form of PVD affects >3 Million people. Within 1 year, 25% of patients die and 30% undergo amputation. We describe a novel technology for generating a therapeutic population (BGC101) of enriched endothelial progenitor cells from a patient’s standard blood sample, using dendritic cells (DCs) to direct stem/progenitor cell (SPC) activity. This one day culture process produces sufficient numbers of potentially therapeutic SPCs for the treatment of patients with CLI who do not have other viable treatment options. The EnEPC-CLI-01 clinical study aims to assess BGC101 feasibility in treating CLI patients. Methods & Results: DCs from healthy and diabetic donors were activated with anti-inflammatory and pro-angiogenic molecules. Co-culture for 12-18 hours of activated DCs with SPCs generated 83.7±7.4×10^6 BGC101 cells with >97% viability and angiogenic/ stemness potential. When administered to nude mice with limb ischemia, BGC101 yielded a high safety profile, improved blood perfusion, capillary density, and limb function within 21 days (p<0.0002). A phase I/IIa Study (open-label in 5 patients followed by randomized placebo-controlled study in 25 patients) is underway. Preliminary results from the first patients demonstrated a high safety profile and promising clinical outcomes. Conclusions: DCs promote the generation of EnEPC within culture after one day. The resulting, BGC101, a potential for treatment of vascular conditions, including arteriosclerotic heart disease, stroke and peripheral ischemia is now undergoing a phase I/IIa study in CLI patients.

Biography:

Arshak R Alexanian is currently the Chief Scientific Officer at Cell Reprogramming & Therapeutics LLC and an Adjunct Associate Professor in the Department of Medicine at the Medical College of Wisconsin (MCW). Previously, he held faculty positions in the Departments of Neurosurgery at MCW (2000-2013) and in the Departments of Anatomy and Neurobiology, as well as in Biochemistry and Molecular Biology, at Colorado State University (1997-2000). He has received training at universities and centers world wide, including the Pasteur Institute and University of Montpelier in France, University of Saarland in Germany, Institute of Biochemistry in China and Russia, and Colorado State University, where he gained extensive experience in the fields of Biochemistry, Molecular Biology, Cell Biology (stem cell biology) and Neurosciences. The areas of interest of his research are the epigenetic regulation of cell fate commitment and differentiation, development of cell reprogramming technologies to produce different neuronal and glial cell types and elucidation of the therapeutic effect of these specialized cell types in several neurological disorders.

Abstract:

Advances in cell reprogramming technologies to generate patient-specific cells of a desired type will revolutionize the field of regenerative medicine. Over the last decade, several cell reprogramming methods such as nuclear transfer, cell fusion and transfection or transduction with pluripotent factors have been developed. However, the majority of these technologies require the exposure of cell nuclei to large reprogramming molecules via. transfection, transduction, cell fusion, or nuclear transfer. These methods raise several technical, safety and ethical issues. Chemical genetics is an alternative approach to cell reprogramming that uses small, cell membrane penetrable substances to regulate multiple cellular processes, including cell plasticity. Recently, using achemical genetics approach (a combination of small molecule modulators of epigenetic target enzymes and neural inducing factors) we have been able to turn human mesenchymal stem cells (hMSCs) directly into neuronal progenitors that have the potential to generate different neuronal subtypes, such as dopaminergic, cholinergic and GABAergic cells when further grown in appropriate neuronal differentiation media. The therapeutic effects of these cells on several neurological disorders have been demonstrated.

Biography:

Abstract:

Measuring gene expression in individual cells is crucial for understanding the gene regulatory network controlling human embryonic development. We applied single-cell RNA -Seq analysis to human preimplantation embryos, primordial germ cells (PGCs),and human embryonic stem cells (hESCs). We also systematically profiled the DNA methylome of human early embryos from the zygotic stage through to post-implantation. We showed that the major wave of genome-wide demethylation is complete at the 2-cell stage, contrary to previous observations in mice. Moreover, the demethylation of the paternal genome was much faster than that of the maternal genome, and by the end of the zygotic stage the genome-wide methylation level in male pronuclei was already lower than that in female pronuclei. Then, we also showed that long interspersed nuclear elements (LINEs) or short interspersed nuclear elements (SINEs) that were evolutionarily young are demethylated to a milder extent compared to older elements in the same family and had higher abundance of transcripts, indicating that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposable elements. Furthermore, we analyzed the DNA methylome of human PGCs andfound global demethylation of their genomes. Approximately, 10 to 11 weeks after gestation, the PGCs were nearly devoid of any DNA methylation, whereas the repeat elements still kept high level of residual methylation. Our work provides insights of critical features of the transcriptome and DNA methylome landscapes of human early embryos and primordial germ cells, as well as the functional significance of DNA methylome to regulation of gene expression and repression of transposable elements.

Speaker
Biography:

Paul J Davis is a Professor of Medicine at Albany Medical College, and Chief Scientific Officer at NanoPharmaceuticals LLC, Rensselaer, NY. He is former Chair at the Department of Medicine, Albany Medical College. As an Endocrine Researcher, he has co-authored 250 scientific publications and has co-edited two text books on Angiogenesis (Springer, 2013; Elsevier, 2016). He and Dr. Shaker Mousa described the thyroid hormone-tetrac receptor on integrin αvβ3.

Abstract:

The programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) immune checkpoint modulates activated T cell-cancer cell interactions. The PD-L1 protein generated by tumor cells engages T lymphocyte PD-1 to suppress T cell engagement of tumor cells—protecting tumor cells from immune destruction—and may also induce T cell apoptosis. Overexpression of PD-L1 is seen in various human cancer cells and correlates with decreased patient survival. PD-1 antibodies (Opdivo®; Keytruda®) are effective anticancer agents in subsets of solid tumor and hematologic malignancy patients. Because these antibodies are effective in subsets of patients and also induce important adverse events (AE) in normal tissues that elaborate PD-L1, it is desirable to seek non-immunologic strategies for attacking the PD-1/PD-L1 checkpoint. We have shown that thyroid hormone (L-thyroxine, T4) at physiological concentrations acts non-genomically to stimulate cancer cell proliferation,to block apoptosis and to stimulate tumor-related angiogenesis. We report here that T4 stimulates PD-L1 gene expression by a mechanism that is initiated at the cell surface receptor for T4 on the extracellular domain of plasma membrane integrin αvβ3. T4 was studied in cultured human colon cancer HT-29 and HCT116 cells and triple-negative breast cancer MDA-MB-231 cells, at concentrations ranging from 10[-8] to 10[-6] M, where 10[-7] M yields physiological concentrations of free T4 in the culture system. T4 significantly increased PD-L1 mRNA abundance by 2-to-6-fold in HT-29 cells, by 2-fold in HCT116 cells and by 1.6-fold in breast cancer cells. An inhibitor of T4 actions at the integrin, tetraiodothyroacetic acid (tetrac), in a nanoparticulate formulation (Nano-diamino-tetrac, NDAT) intended to increase tetrac residence time at the integrin, blocked the actions of T4 on PD-L1 gene expression and significantly reduced basal PD-L1 expression. Basal expression is defined here as that which occurs in the absence of added T4. T4 also significantly increased PD-1 mRNA abundance in these tumor cell lines and NDAT blocked the T4 effect and significantly reduced basal levels of PD-1 mRNA. PD-1 is viewed primarily as T cell product, but has been reported to be expressed by a variety of solid tumor cells and we speculate in such cells, which may be anti-apoptotic. In summary, the components of the PD-1/PD-L1 check point are subject to non-immunologic modulation by T4 and by NDAT. The actions of NDAT in these in vitro studies have possible therapeutic implications