8th World Congress and Expo on Cell & Stem Cell Research March 20-22, 2017 Orlando, Florida, USA

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 of over a dozen of worldwide patents, Founder and CEO/CSO of FasCure Therapeutics, LLC. He widely published, organized and lectured at numerous national/international conferences, served on study sections for various federal and non-profit funding agencies, and is the Editorial Board Member of a number of scientific journals. He is the member of several national and international societies and recipient of various awards.

The costimulatory members of the TNFR family molecules are critical for the generation of cellular and humoral immune responses. In particular, the 4-1BB pathway regulates various cells of innate, adaptive, and regulatory immunity for a productive immune outcome. As such, the ligand, 4-1BBL, has a great potential as adjuvant component of prophylactic and therapeutic vaccines against cancer and infections. We generated a novel form of the ligand, SA-4-1BBL, and demonstrated its pleiotropic effects on various cells of the immune system. As adjuvant, SA-4- improved the protective efficacy of the lead rF1V subunit vaccine against Y. pestis in a mouse model by generating mixed Th1 cellular and humoral immune responses.

Cancer-associated fibroblasts (CAFs) are one of the most abundant non-cancer cells in the tumor microenvironment that support melanoma to grow, migrate and develop drug resistance. β-catenin signaling is important for fibroblast activation and their biological functions. We discovered that CAFs that surround and infiltrate melanoma tumors express high levels of cytoplasmic and nuclear β-catenin. Ablation of β-catenin causes cell cycle arrest in stromal fibroblasts and reduces the production of autocrine and paracrine factors and extra cellular matrix (ECM) proteins. Thus, we designed a novel genetic approach to ablate β-catenin expression in melanoma-associated CAFs to evaluate their effects on the initiation and development of Braf-driven melanoma. To our surprise, stromal fibroblasts showed inhibitory effects on melanoma initiation in vivo. Conversely, Braf-activated Pten-deficient melanoma development was significantly suppressed after CAFs were deactivated by β-catenin ablation. Consistent with this observation, melanoma cell growth was significantly inhibited while cell death was increased. Meanwhile, decreased production of ECM protein collagen and fibronectin was found in Braf-driven melanoma tumors that contained β-catenin-deficient CAFs, suggesting the melanoma microenvironment was remodeled. Further analysis revealed that expression of phospho-Erk1/2 and phospho-Akt was greatly reduced, effectively abrogating the activating effects and abnormal cell cycle progression induced by Braf and Pten mutations. In addition, epithelial-mesenchymal transition (EMT) was also suppressed in melanoma cells. Taken together, our data highlight an important crosstalk between CAFs and the RAF-MEK-ERK signaling cascade in BRAF-activated melanoma and may offer a new approach to abrogate host-dependent drug resistance in targeted therapy.

Thomas Andl obtained his PhD from the University of Heidelberg, Germany and extended his training in squamous epithelia and hair follicle biology at the University of Pennsylvania and Vanderbilt University. He established mouse models to study BMP, Wnt and microRNA signaling and is interested in how squamous epithelia such as the epidermis or the oral mucosa are maintained under normal conditions and how these epithelia responds to stress, infection and carcinogenesis. His main focus is on the putative stem cells in these tissues and how they are organized, maintained, transformed into cancer and are responding to challenges.

Adult tissue stem cells maintain tissues throughout life. Therefore, there may be quantitative and qualitative differences in the stem cells of short-lived and long-lived mammals. We hypothesized that one adaptation to longevity could reside within the stem cell compartment, e.g. by enhancing the quality and integrity of the stem cell pool through increased stem cell quiescence and repair. Using squamous epithelia as model systems to explore our stem cell quality-longevity hypothesis, we show that the pattern of proliferation in human oral mucosa fundamentally differs from most other mammals. In contrast to mouse squamous epithelia, proliferation in humans is absent from the basal cell layer and over 90% of proliferating cells are found in the first suprabasal cell layer(s). Therefore, human squamous epithelia have a quiescent basal cell layer that traditionally is viewed as the stem cell layer. The relative proliferative activity of the basal cell layer is correlated with short-livedness in mammals and basal cell quiescence to our knowledge is the only other characteristic that correlates with longevity in addition to body size. Next, we defined the characteristics of this quiescent basal cell layer. Key features in addition to its quiescence are TGF beta expression signatures, polycomb repressor complex 1 (PRC1) expression, expression of a set of well know apoptosis protectors and Hippo signaling components. In a 3D squamous epithelial reconstruct TGF beta signaling was able to induce quiescent basal cell markers supporting a role of this signaling pathway in establishing or maintaining quiescent stem cells in human squamous epithelia.

George G Chen is a Professor in the Department of Surgery, Director of Surgical Research Laboratories, The Chinese University of Hong Kong, China. He has extensive experience in cancer research, particularly in the area of hepato-carcinogenesis. He has authored or co-authored more than 190 papers and has written number of books or book chapters.

Clinically, hepatocellular carcinoma (HCC) occurs much more frequently to males than females, but, the underlying mechanisms remain largely unknown. Cytochrome P450 1A2 (CYP1A2) is involved in the metabolism of 17β-estradiol (E2) that is known to have a protective role in the development of hepatocellular carcinoma (HCC). In this study, experiments were carried out in cultured HCC cells and animal models to explore the significance of CYP1A2 in HCC. It was found that the level of CYP1A2 was significantly reduced in HCC. The overexpression of CYP1A2 could inhibit the growth of HCC in cultured HCC cells as well as the HCC tumor model in mice. Mechanically, the hypermethylation of the CYP1A2 promoter contributed to its reduction and the application of HDAC inhibitors recovered the loss of CYP1A2. In conclusion, the expression of CYP1A2 was significantly reduced in HCC and this reduction can be corrected by the inhibition of HDAC.

Purwati has finished in general practitioner from Airlangga University in 1997, has completed in internal med. Specialist in 2008 from Airlangga University also and taken Doctoral program in Airlangga University 2010-2012. Interest in stem cell field from 2008, be secretary of stem cell laboratory of Airlangga University and also secretary of Surabaya Regenerative Medicine Centre. 2015 be a chairman of stem cell research and development Centre Universitas Airlangga Surabaya Indonesia. Have almost 50 publication in journals, papers, and seminar.

Infectious diseases still remains a health problem in both developing and developed countries. Based on epidemiological studies that have been conducted, sepsis is known as a major health problem, because it is still the leading cause of death in critical cases in the world. Dr. Soetomo Hospital reported that 32.18% new visitors are infected (Health Status Profile of East Java Province). In a research done at Dr. Moewardi Hospital in 1997, about 130 (97%) from 135 sepsis patients died, while at the Internal Medicine Dr. Moewardi Hospital in 2004, it was 74 (83.1%) patients. Armstrong and Pinner (1999) reported that recently in USA, there is an increase in the proportion of patients hospitalized for infection and mortality rate of infectious diseases. Three indicators that show an increase in the burden of infection are high mortality in infectious diseases, the proportion of infectious diseases hospitalization, and the number of ambulatory patients with infectious diseases. The most sepsis causes are derived from a toxin balk stimulation of gram-negative endotoxin or gram-positive exotoxin. Endotoxin can directly cause sepsis by the Lipo Poly Saccharide (LPS) and along with antibodies in the patient's blood serum form LPSab (Lipo Poly Saccharide antibody). LPSab in blood through the receptor CD14+ will react with macrophages. Makropfag will express Immunomodulatory IL-1, TNF-α, IL-6 and IL-8, which cause an inflammatory reaction. These reactions can only occur on gram-negative bacteria which have LPS on the walls. Stem cell therapy for sepsis includes Mesenchymal Stem Cells (MSCs) and Haematopoetic Stem Cells (HSCs), both types of stem cells as an immunomodulator in sepsis. MSCs inhibit maturation and decrease the expression of molecules presentation and co-stimulator from cells presenting antigen. MSCs also inhibit B-cell antibody production. In case of NK cells, MSCs can suppress proliferation, cytokine secretion and cytotoxicity. Furthermore, MSC does not only have the obstacles effect directly in T cells, but also affects the first critical stage of the immune response in which MSC can inhibit the differentiation and maturation of cells presenting antigen and causes dendritic cells to change the cytokine secretion profile to reduce secretion of proinflammatory cytokines such as TNF-α, IFN-γ and IL-12. The most important thing is to increase the production of IL-10, that is suppressive and tolerogenic and is a potent inducer of regulatory T cells (Treg). In addition, it has been reported that human MSC causes an increase in the proportion of Treg.

Kenneth K Wu, MD, PhD was the Professor and Director of Hematology and Vascular Biology Research Center at University of Texas Health Science Center at Houston, Texas, USA and served as the President of National Health Research Institutes of Taiwan. He is currently Chaired Professor at China Medical University (CMU) Taichung, Taiwan and National Tsing-Hua University Hsin-Chu, Taiwan. He has published more than 350 papers and served as Editorial Board Member or Associate Editor of several journals.

Premature senescence of Mesenchymal Stem Cells (MSCs) contributes to MSC growth arrest and secretory phenotype. It hampers MSC expansion in culture and MSC cell therapy. To develop strategies to prevent MSC senescence, we assessed 5-methoxytryptophan (5-MTP). We previously reported that human fibroblasts and endothelial cells produce and release 5-MTP into the extracellular milieu including circulating blood. Serum 5-MTP concentrations in healthy human subjects were 0.5-1.2 μM. 5-MTP inhibits stress-induced cyclooxygenase-2 (COX-2) and cytokine expressions in macrophages and protects endothelial barrier function and integrity. To determine whether 5-MTP controls MSC senescence, we pretreated bone marrow-derived MSC (BMMSC) with chemosynthetic pure L-5-MTP followed by high glucose (HG) or H2O2. HG metabolic stress or H2O2 oxidant stress induces typical premature senescence such as growth arrest, increased p16 and p21, SA-βgal and senescence-associated secretory phenotype (SASP). 5-MTP prevented all the senescence phenotypes induced by HG or H2O2. Our preliminary data suggest that 5-MTP exerted the anti-senescence effect by upregulating Foxo3a expression. We conclude that 5-MTP is a valuable lead compound to develop new agents to prevent MSC senescence and improve MSC cell therapy.

Yoshiaki Ito has obtained his MD and PhD from Tohoku University, Japan and studied in Duke University, USA, Imperial Cancer Research Fund Laboratories, UK and NIH, USA. He became Professor in 1984 in the Institute for Virus Research, Kyoto University and served as Director between 1995-2001. In 2002, he moved to the Institute of Molecular and Cell Biology in Singapore and also served as Director of Oncology Research Institute, National University of Singapore (NUS) between 2002 and 2008. He is currently a Senior Principal Investigator at the Cancer Science Institute of Singapore, NUS. He discovered the middle T of polyomavirus and RUNX gene.

The understanding of gastric carcinogenesis is still relatively poor, because of the lack of knowledge of stem cells in stomach. Stomach is roughly divided into the corpus (main body) and antrum (next to duodenum). Rapidly growing cells are located in the isthmus of both corpus and antrum. We reported earlier on the 270 bp RUNX1 enhancer element that drives the expression of RUNX1 in hematopoietic stem cells (HSC), termed eR1. We now show that eR1 also targets isthmus of both the corpus and antrum. A well-known stem cell marker, Lgr5 was reported to identify stem cells of stomach but never in the isthmus. In the antrum, Lgr5+ cells are located at the base of antrum below the location where eR1+ cells reside. Both Lgr5+ cells and eR1+ cells have the ability to form organoids which are considered to develop only from stem cells. I will discuss about the presence of more than one stem cell types in a given tissue. Small number of eR1+ cells is also detected in fully differentiated chief cells that express pepsinogen located at the base of corpus. There are several reports showing the ability of chief cells to proliferate. Currently, there are disagreements among the researchers as to whether chief cells have potential to have stem cell activity. The consequence of K-rasG12 expression in eR1+

cells will also be discussed.

Ganapathi Bhat M is a Senior Consultant Medical Oncologist & Stem Cell Transplant Physician at Jaslok Hospital & Research Centre, since 2006. He gained specialized training in stem cell transplantation as part of the ESH-EBMT (2007), 2011 (Labaule, France) and ICAS training program (2009) from ULM University, Germany. He is also a Member of academic organizations namely ESMO, IELSHG, EHA, Asia Pacific Bone Marrow Transplant and an Affiliate of American Association for Cancer Research and BITs Congress Tank. He served on the board of teaching faculty (Kuwait) for MRCP (Pathology & Hematology). He is also an Editorial Board Member of various international scientific journals.

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) intents at abating malignant and benign diseases. However, Graft-versus-host disease (GVHD) still is the major cause of morbidity and mortality. GVHD demonstrates a heterogeneous clinical presentation and compromises the benefits associated with allo-HSCT. The complex pathophysiology of GVHD remains as a focus of unending research and it also outlines many existing and novel therapeutic targets. This has become a major objective of research in the transplant immunobiology. Standardized stratagem to understand the predisposing factors, pathophysiology and diagnosis for both acute and chronic forms of the disease, is still lacking. There is a need for better insight into the Pathobiology behind the GVHD process and widening more effective treatment strategies while maintaining the graft versus tumor effect to keep away a likely rise in relapse-related mortality. The studies should be directed towards assessment tools for disease severity, outcome, quality of life; variability factors influencing the outcome of the transplant and identification of potential biomarkers which predicts therapeutic responses as both acute and chronic GVHD are biologically and clinically heterogeneous. The increasing knowledge about host as well as the donor associated variables that aggravate GVHD and to develop drugs in relation to immune-modulation perhaps allows more effective treatment of GVHD in the future. Impending research strategies and the discovery of novel therapeutic targets may improve the outcome further. Well timed diagnosis, multidisciplinary working and good supportive care are undoubtedly important to optimize the response and survival.

Mahsa Rashidi is MD, PhD at Children’s National Hospital, DC, affiliated to George Washington University of Medical Sciences, USA. She has finished her Medical degree at Shahid Beheshti University of Medical Sciences, Tehran, Iran. Her PhD is a joint program between George Washington University, USA and the University of Melbourne, Australia. This abstract is based on her PhD thesis, submitted to the University of Melbourne, Faculty of Medicine, Australia. Her work is focused on evaluating skin-stem-cells for cell-based therapies in muscular dystrophies. In her work, the effects of various dosages of several drugs/treatments on the stem cells differentiation is evaluated.

Duchenne-muscular-dystrophy (DMD) is the commonest muscular-dystrophy caused by the absence of dystrophin. Stem-celltherapy in DMD is one of the more promising-approaches for treatment. Multipotent-stem-cells residing in the hair-folliclepapilla are highly-plastic and are reprogrammable to bone, cartilage, haematopoietic and muscle. Dermal-papilla-cells (DPC) from the hair-follicles of mouse-whisker-pad were microdissected and cultured. We showed that DPC undergo myogenic-differentiation when co-cultured with different types of myoblasts including normal and dystrophic human-myoblasts. Lamin A/C staining was used to distinguish DPC and myoblast-derived myonuclei inside myotubes. DPC incorporated into myotubes and up-regulated the muscle-marker myogenin in co-culture with human-myoblasts, suggesting that DPC fully underwent myogenic-differentiation in these co-cultures. DPC incorporation-efficiency was low in all co-cultures and differed significantly between various types of myoblast; however, no significant difference was observed between normal and dystrophic human-myoblasts. These encouraging-findings suggested that the altered properties of dystrophic-myoblasts did not compromise the myogenic-differentiation of DPC in-vitro,supporting their in-vivo application and possible therapeutic-potential. The in-vitro effects of galectin-1, reversine and activation of the Shh signaling-pathway via. recombinant Shh and purmorphamine, on DPC myogenic-differentiation was also evaluated. None of the treatments increased myogenin-expression in DPC; but, triggering Shh-signaling produced a dose-dependent-pattern, whereby lower-levels of signaling promoted myogenic-differentiation while higher-levels inhibited it. Activating Shh-signaling upstream of Smo via. purmorphamine, induced a biphasic differentiative-response; however, the application of rShh hindered the differentiation of both cell types. Thus, murine-DPC are a readily-accessible-source of stem-cells that can undergo myogenic-differentiation in-vitro. We aim to improve their differentiation-efficacy to make them suitable-candidates for therapeutic-applications in muscle-wastingdisorders.

Dr. Medet Jumabay has been serving as a doctor and researcher in the field of cardiovascular medicine for more than twenty years. Dr. Medet Jumabay has graduated from medical school and started her medical career at the Emergency Center of the First Affiliated Hospital of Xinjiang Medical University. Later she became an attendant physician and cardiologist in the department of medicine at the same university. Dr. Medet Jumabay received her Master’s degree from the Xinjiang Medical University and a PhD. degree from the Department of Medicine, Nihon University, Tokyo, Japan in medical science. Dr. Medet Jumabay first became fascinated by the power of cell plasticity when she saw beating cardiomyocytes, which are derived from adipose stem cells. Thus, she became interested in cell regeneration research immediately after completing her PhD. studies. In 2007, she was recruited to the Division of Cardiology, Department of Medicine, UCLA, as a researcher in the field of cardiovascular and stem cell biology.

The ability to identify an ideal cell source for tissue regeneration is still challenging researchers in the stem cell field. The possession of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and may have clinical, biochemical or molecular implications. Adaptation of stem cells from adipose tissue to use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipid-free multipotent cells, referred to as dedifferentiated fat (DFAT) cells. Compared with other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro or in vivo, the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potential. In addition, DFAT cells at early stage, spontaneously exhibit a high degree of pluripotency, which was responsive to changes in culture conditions and may benefit cell-based therapies. Thus, mature white adipocytes may be a new cell source for tissue regeneration. The unique features of DFAT cells are promising for clinical applications such as regenerative medicine.

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.

Lithium (Li) salts have been widely used in psychiatry as mood stabilizing agents for 60 years. Li found in variable amounts in foods, especially grains, vegetables, and in some areas, the drinking water provides a significant source of the element. Therefore, dietary intake in humans depends on location, type of foods consumed, and fluid intake. Traces of Li have been detected in humanorgans and tissues, leading to speculation that the element was responsible for specific functions in the human body. It was not until the 20th century that studies performed in the 1970’s and 1990’s, primarily in rats and goats, maintained on Li-deficient diets demonstrated higher mortality, altered reproductive and behavioural abnormalities. Such deficiencies have not been detected in humans; however, studies performed on populations living in areas with low Li levels in water supplies have been associated with higher rates of suicides, homicides, and the arrests rate for drug abuse and other crimes. Li appears to play a significant role in early fetal development as evidenced by high Li levels during the early gestational period. Biochemically, the mechanism of Li action involves multi-factor and interconnected pathways with enzymes, hormones, vitamins, and growth and transforming factors. Thisody of evidence now appears sufficient to label Li as an essential element with the recommended RDA for a 70 kg adult of 1000 mg/day. Of extreme importance for the future is the growing body of evidence indicating Li can be used effectively for the treatmentof acute brain injuries, e.g., ischemia and chronic neurodegenerative dis- eases such as Alzheimer’s disease, Parkinson’s disease, Tauopathies, and Huntington’s disease. This conclusion is based upon evidence showing Li as important in neurogenesis as well as protecting neurons from neurotoxicity. Li influences stem cells, both neuronal and marrow derived, thus, the additional therapeutic implications for this element in clinical medicine to treat disorders associated with the faulty production of blood and nerve cells or as a tool to enhance blood stem cell mobilization for transplantation are needed.

Maliheh Nobakht is a full Professor of Medical Histology and Embryology in Iran University of Medical Sciences. She is a board certified Histologist and Embryologist and is engaged in education and is a basic Science Scientist known an Investigator at Iran University. She has expertise in wound healing and stem cell biology, scaffold and Neuroscience. She graduated from Tehran University in 1985, with a Bachelor of Science degree in Biology. Then, she received Master of Science degree on Histology and Embryology in 1987. She received her PhD degree from Tarbiat Modarres University on Histology in 1992. Subsequently, in 1994, she completed her Post-doctoral training in Molecular Biology and Electron Microscopy under supervision of Professor Leblond and Dr. Lee at McGill University and Shriner's Hospital in Montreal, Quebec, Canada. She became a full Professor in Histology Medicine in 2011 and at the same time, she was appointed to be the Co-director of the vice of education.

Introduction: The main aim of medicine is Wound healing in a shorter time and with fewer side effects. Cell therapy, especially treatment with stem cells has become as a possible solution for wound healing. In this study we evaluate the effect of hair follicle stem cells transplantation and SDF-1/CXCR4 axis in cutaneous wound healing in Rats. Materials and Methods: Animals (male Wistar rats) were divided into five groups: 1) Control (non-treated), 2) Vehicle (PBS), 3) AMD (treated with AMD), 4) HFSCs treated with AMD) , and 5) HFSCs (treated with HFSCs). (AMD is inhibitor of SDF-1/CXCR4 axis). The Bulge region of rat whiskers was isolated and cultured in DMEM/F12. Then transplanted to wound site. At the end of the treatment period, histological assessments (H&E, Masson's trichrome staining), and molecular assays (ELISA, q- PCR) were performed. Results: The diameter of epidermis, Amount of collagen, wound healing percent as well as expression of SDF-1, CXCR4 and VEGFR2 in HFSCs groups were significant compared with control group (P<0.05). In AMD group, these parameters were significantly low compared with control group (P<0.05). Conclusion: Transplantation of hair follicle stem cells had potential capability for cutaneous wound healing in Rats. However with increasing the SDF-1 expression level in in the injured area, HFSCs can recruit other stem cells and contribute to wound repair with

SDF-1/CXCR4 axis.

Human bone morphogenetic protein 2 (hBMP2) through the other BMPs group family has been shown to have a significant role in regulating the odontogenic differentiation of dental tissue-derived stem cells. However, there are few studies on the effects of the BMP2 gene on the proliferation and odontogenic differentiation of human dental pulp stem cells (hDPSCs). DPSCs have many advantages in comparison to other types of dental stem cells including easy to access for isolation, high proliferation capacity, extensive capability to produce mineralized matrix and similarity to bone marrow MSCs phenotype. This study evaluated in vitro odontogenic differentiation potential of lentiviral-mediated BMP2 gene-transfected human DPSCs. DPSCs were isolated by enzymatic dissociation of primary and permanent teeth. The characteristics of DPSCs was evaluated by flow cytometry (FCM) then transduced with lentiviral vector to secretion of BMP2 along with expression level of green fluorescent protein (GFP). Transduced cells were analyzed for BMP2 secretion with RT PCR. Almost 70% of human dental pulp stem cells could express GFP marker following transduction. Graphical analysis and GFP assay confirmed BMP2 expression level in DPSCs transduced by recombinant lentiviral vectors was 6 times more than the native DPSCs. This result showed the induction odontogenic potential in DPSCs. In conclusion, DPSCs could be considered as one of the promising sources for tissue engineering including potential application for dental tissue, nerve and bone regeneration after tooth extraction or diseases and maxillofacial treatment failure. However, further studies should be performed to confirm this hypothesis. Also, lentiviral-mediated BMP2 gene transfection could enhance the in vitro odontogenic differentiation capacity of human DPSCs.