Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 10th World Congress and Expo on Cell & Stem Cell Research New York, USA.

Day 1 :

Keynote Forum

Haval Shirwan

University of Louisville, USA

Keynote: Induction of tolerance to allogeneic islet grafts using an immunomodulatory biomaterial

Time : 09:30-10:00

OMICS International Stem Cell Research 2018 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:

Type 1 diabetes (T1D) is a chronic autoimmune disease that impacts millions of people world-wide. Presently, there is no cure for T1D and treatment with exogenous insulin to manage diabetes is ineffective in controlling euglycemia in a substantial population of type 1 diabetics.  Transplantation of pancreatic islets as a source of beta cells producing insulin has proven effective in improving metabolic control in type 1 diabetic individuals. However, graft rejection is a major limitation of clinical islet transplantation that is controlled by chronic immunosuppression. Systemic use of immunosuppression is associated with various adverse effects that compromises the life quality of graft recipients.  We have been pursuing the development of targeted and localized immunomodulatory approaches as a safe and effective alternative to chronic immunosuppression. In particular, we developed biomaterials based on polyethylene glycol microparticles engineered with immunomodulatory ligands targeting islet destructive pathogenic T effector cells for physical elimination within the graft microenvironment. The application of this novel concept to the induction of tolerance to islet allografts as a cure for T1D will be discussed. 

OMICS International Stem Cell Research 2018 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:

Keynote Forum

Diana Anderson

University of Bradford, UK

Keynote: Oxaliplatin-induced Oxidative Stress in Isolated Spermatogonial Stem cells

Time : 10 :30-11:00

OMICS International Stem Cell Research 2018 International Conference Keynote Speaker Diana Anderson photo
Biography:

Diana Anderson (H index 54) holds the Established Chair in Biomedical Sciences at the University of Bradford. She obtained her first degree in the University of Wales and second degrees in the Faculty of Medicine, University of Manchester. She has 450+ peer-reviewed papers, 9 books, has successfully supervised 30 PhDs, is an Editorial Board Member of 10 international journals. She is Editor-in-Chief of a book series on Toxicology for the Royal Society of Chemistry. She gives key note addresses at various international meetings. She is a consultant for many international organisations, including WHO, EU, NATO, TWAS, UNIDO, OECD.

Abstract:

Spermatogonial stem cells (SSCs) are responsible for transmission of genetic information from males to their progeny. SSCs play pivotal roles in spermatogenesis and reproductive biology of gametes and treatment of infertility. Many chemicals have a negative impact on the SSCs, either directly, or indirectly through the somatic nursing cells. Eventually, these effects can inhibit fertility, and they may have negative consequences for the development of the offspring. Oxaliplatin is a platinum-organic drug with antineoplastic properties used for colorectal cancer and cytotoxicity due to platinum binding to DNA and the formation of intrastrand cross-links between neighbouring guanines. This study was to establish an oxidative stress model for antioxidant activity of some drugs investigated in SSCs in in vitro culture. The effects of oxaliplatin on SSCs were evaluated by standard cytotoxicity assays and the potential biochemical and molecular effects on the antioxidant system. Administration of oxaliplatin showed significant increases in DNA damage, p53 and bcl-2 gene expression levels concomitant with significant decreases in endogenous antioxidant enzymes SOD, CAT and GPx-mRNA gene expression. Glial cell line–derived neurotrophic factor (GDNF) is important for SSC self-renewal in vitro and in vivo, so we also assessed oxaliplatin on GDNF-mediated signalling in these cells and oxaliplatin significantly decreased GDNF-mRNA and associated protein. Oxaliplatin-induced DNA damage causes an increase in intracellular superoxide anions which are reduced by the exogenous antioxidant flavonoid, quercetin. This study highlights evidence that SCCs have antioxidant and antiapoptotic properties that could reverse oxaliplatin-induced testicular toxicity, in addition to their role in spermatogenesis.

Keynote Forum

Jack A Coleman

The Lung Health Institute, USA

Keynote: Cell therapy for chronic lung disease

Time : 11:20-11:50

OMICS International Stem Cell Research 2018 International Conference Keynote Speaker Jack A Coleman photo
Biography:

Jack A Coleman has earned his MD from the University of Cincinnati College Medicine in 1979, did his internship and General Surgery requirement at Cincinnati General Hospital and residency in Otolaryngology - Head and Neck Surgery at the University of Pittsburgh Eye and Ear Hospital as well as a fellowship at English Plastic and Cosmetic Surgery Center. He has been an Assistant Professor at Vanderbilt University and Clinical Assistant Professor at Eastern Virginia Medical School. Currently he is National Medical director for the Lung Institute. He has published over 23 articles in refereed journals, many book chapters and 5 books related to his various interests in medicine as well as national and international guest lecturer.

Abstract:

 

The Lung Health Institute has been treating chronic lung diseases with regenerative therapy for over four years and has treated over 5,000 patients. The diseases treated are in two broad categories: chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). The common factor in these diseases that the treatment addresses is chronic inflammation. Up to this point these diseases have been treated with symptomatic control only with lung transplant being the only “curative” therapy. By utilizing autologous cells and Platelet Rich Plasma (PRP) the disease progress can be positively affected in the majority of patients treated. The cells and cytokines used will be reviewed as well as proposed mechanisms of action. Protocols utilized for the treatment will be reviewed along with changes that have been made over time. Two studies have been completed and will be summarized. The first is a review study of 568 patients with COPD treated in 2015. Self-reported quality of life measures using the Clinical COPD Questionnaire and pulmonary function tests were measure before treatment and 6 months after. 73% of patients had positively affected quality of life scores and no significant changes were noted in the PFT scores. The second study is a prospective study of 207 patients with COPD (167) or ILD (40). 124 patients completed the 6 month study period. Paired sample T-tests were used for data analysis. 90/124 reported CCQ score unchanged or improved (72.5%), increases of greater or equal to 0.4 (considered significant change for CCQ) was 61/124 (49.2%). We will also discuss need for further testing such as randomized control studies and review potential new therapies to improve treatments for these patients.

Keynote Forum

J. Koudy Williams

Wake Forest Baptist Medical Center, USA

Keynote: Optimizing regenerative medicine therapies for differing patient populations

Time : 11:50-12:20

OMICS International Stem Cell Research 2018 International Conference Keynote Speaker J. Koudy Williams photo
Biography:

J Koudy Williams is a DVM with over 35 years of experience in performing translational research using different animal models of human disease. He has published over 120 full length manuscripts and 20 chapters and reviews. His focus is on women’s health and recently on Regenerative Medicine approaches to restoration of the urinary sphincter for women with urinary incontinence.

Abstract:

Regenerative Medicine offers the promise of an unlimited amount of tissue and organ repair and replacement. Great progress has been made in preclinical studies and many applications are now in the clinical stage. Regenerative Medicine is beginning to explore the potential effects of efficacy in different patient populations. The risk urinary incontinence in women is age and obesity related, and is a chronic disease influenced by the sex hormone milieu. It is well known that aging and diabetes reduce the ability of tissue to regenerate. It also stands to reason that these changes may also influence the efficacy of Regenerative Medicine approaches to urinary incontinence. In fact, this may explain, in part, why cell therapies for urinary incontinence are so successful in preclinical studies (which historically use younger health animals with acute UI)? In contrast, the results of clinical studies in older women with varying body weights, sex hormone status and chronicity of disease. This presentation will first review select studies identifying the effects of age, gender and hormone status on the ability of cells to stimulate regeneration of tissues. The majority of this presentation will introduce a female nonhuman primate (NHP) model of induce intrinsic urinary sphincter deficiency (ISD) and then present results of several studies describing the effects of skeletal muscle precursor cell (skMPC) treatment in acute vs. chronic fibrotic ISD; older and younger NHPs and in NHPs with stress-induced dysmenorrhea. The presentation will close with the results of recent studies identifying the use of chemokines on sphincter regeneration in this animal model. 

Keynote Forum

Esmaiel Jabbari

University of South Carolina School of Engineering, USA

Keynote: 3D micro-patterned co-culture of mesenchymal and endothelial stem cells for concurrent induction of vasculogenesis and osteogenesis

Time : 12:20-12:50

OMICS International Stem Cell Research 2018 International Conference Keynote Speaker Esmaiel Jabbari photo
Biography:

Esmaiel Jabbari has completed his PhD at Purdue University and Post-doctoral studies at Monsanto, Rice University, and Mayo Clinic. He is the Director of Tissue Engineering and Drug Delivery Laboratory and Full Professor of Chemical and Biomedical Engineering at University of South Carolina. He received the Berton Rahn Award from AO Foundation in 2012 and the Stephen Milam Award from Oral and Maxillofacial Surgery Foundation in 2008. He was elected to the College of Fellows of AIMBE in 2013. He has published >250 peer-reviewed articles and presented >260 conference lectures. He serves as Academic Editor of PLOS ONE.

Abstract:

Osteogenesis and vascularization during development are coupled by spatiotemporal regulation of paracrine signaling in which the invading vascular endothelial progenitor cells secrete osteogenic morphogens to stimulate cell differentiation and bone formation. Conversely, the committed mesenchymal stem cells (MSCs) in the vicinity of the vascular endothelial cells release vasculogenic morphogens to further stimulate vasculogensis for the metabolically highly active osteoblasts. The objective of this work was to investigate the effect of micro-patterning of mesenchymal stem cells (MSCs) and endothelial colony forming cells (ECFCs) within a 3D hydrogel matrix combined with localized delivery of osteogenic and vasculogenic morphogens BMP-2 and VEGF on synergistic expression of paracrine signaling factors and coupling of osteogenesis and vasculogenesis. Human MSCs and sustained release BMP-2 nanogels were encapsulated in a slow-resorbing polyethylene glycol-based hydrogel matrix containing micro-channels. Next, a combination of human MSCs, human ECFCs, and on-time release VEGF nanogels were delivered to the micro-channels of the matrix in a fast-resorbing galatin-based hydrogel. This approach resulted in spatial patterning of MSCs and ECFCs and spatiotemporal delivery of BMP-2 and VEGF morphogens. The effect of cell and morphogen patterning on vascularized osteogenesis and paracrine signaling was assessed by biochemical, mRNA, protein analysis, and immunofluorescent staining. The localization of MSCs to the matrix and MSCs+ECFCs to the microchannels combined with temporal release of BMP-2 in the matrix and VEGF in the channels sharply increased the expression of paracrine signaling factors basic fibroblast growth factor (bFGF, vasculogenic and osteogenic), platelet-derived growth factor (PDGF, vasculogenic), and transforming growth factor-beta (TGF-β, osteogenic) by the encapsulated human MSCs and ECFCs. These results suggest that osteogenesis and vascularization are coupled by localized secretion of paracrine signaling factors by the differentiating MSCs and ECFCs.

Keynote Forum

Bruce K Young

New York University, USA

Keynote: Clinical potential of stem cells in human amniotic fluid

Time : 12:50-13:20

OMICS International Stem Cell Research 2018 International Conference Keynote Speaker Bruce K Young photo
Biography:

Bruce K. Young is a graduate of Princeton University and New York University School of Medicine. He is internationally known as a leader and innovator in Obstetrics and Gynecology.  His  122 peer-reviewed publications report various fetal heart rate patterns and their relationship with fetal acid base metabolism and adverse neonatal outcome, referred to in the major obstetrics textbooks, estriol conjugates in amniotic fluid as a marker of fetal kidney function, fetoscopic surgery, risk assessment for high risk pregnancies, incompetent cervix, recurrent miscarriage, the fetal immune system, maternal-fetal immunologic cross-talk, and currently, human amniotic fluid derived stem cells. He has edited 2 books on Maternal-Fetal Medicine and written 2 books for the general reader.  He is a member of the Helen Kimmel Srem Cell Research Center, emeritus Director of the New York University-Langone Medical Center Division of Maternal-Fetal Medicine and presently directs the Pregnancy Loss Prevention Center there.

 

 

 

Abstract:

Amniotic fluid cells from second trimester amniocentesis(hAFSC) have been found to be a source of multipotent stem cells which might overcome the limitations of expansion, histocompatibility, tumorigenesis and ethical issues associated with the use of human embryonic cells. Previous work by others demonstrated pluripotency and growth patterns in c-Kit selected cells. We sought to perform a more comprehensive investigation of their  pluripotency  and the culture characteristics and distribution of stem cell markers in c-Kit selected cells compared to c-Kit negative cells.  Using MACS & FACS we found less than 5% of HAFSC were c-Kit positive. However when cultured,  between 15-90% of the c-Kit negative cells expressed CD90, SSEA4 or TRA-1-60, in varying amounts . There was persistence of stem cell markers including expression of SSEA4, TRA-1-60, CD90 in vitro through multiple passages and subpopulations in a high percentage of cells. There was increased Oct4, Nanog and Sox2 mRNA expression in cells derived from 15-17 gestation week amniotic fluid samples versus longer gestational ages. Double and triple labeled cell populations were identified by MACS .  5.5% of c-Kit negative cells were triple positive for SSEA4, TRA-1-60 and CD90 expression. This may be a more efficient method than c-kit selection of hAFSC  because  stem cell markers expression was equal to or exceeded by the c-kit negative cells in our results. Differentiation of amniotic fluid cells was successfully induced for neural, bone and cartilage lineages using specific induction media as demonstrated by morphologic staining and fluorescent histochemistry. The occurrence of triple-labeled cell populations poses the intriguing possibility of cells with a closer resemblance to embryonic stem cells.  Our results confirm  that hAFSC  maintain pluripotency markers in culture over enough passages to provide sufficient numbers of cells for clinical use.  Current studies with serum-free media  offer  therapeutic promise.

 

Keynote Forum

Mari Dezawa

Tohoku University Graduate School of Medicine, JAPAN

Keynote: Endogenous reparative muse cells may provide novel therapeutic approaches

Time : 14:10-14:40

OMICS International Stem Cell Research 2018 International Conference Keynote Speaker Mari Dezawa photo
Biography:

Mari Dezawa is graduated from Chiba University School of Medicine in 1989, and got PhD degree in 1995 at the same institution. She moved to Yokohama City University as Assistant Professor of Dept Anatomy in 2000 where she started to work with mesenchymal stem cells (MSCs). After moving to Kyoto University Graduate School of Medicine as Associate Professor in 2003, she discovered methods to induce neurons and skeletal muscle cells from human MSCs. In 2008, she became Professor and Chair of Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, where she discovered muse cells (PNAS, 2010, PNAS, 2011, Nat Protocol, 2013, JASN, 2017). 

Abstract:

Multilineage-differentiating stress enduring (muse) cells are naturally existing unique endogenous stem cells that are non-tumorigenic and are pluripotent-like. They express pluripotent markers, can generate cells representative of all three germ layers from a single cell and are able to self-renew. Since they express specific receptor for damage signal, they can preferentially home into damaged site after topical injection or intravenous injection with lower entrapment in the lung and spleen. After integration, they replenish lost cells by spontaneous differentiation into tissue-compatible cells, leading to robust tissue and functional regeneration. The unique reparative functions of Muse cells were demonstrated in animal models of liver cirrhosis, partial hepatectomy, stroke, skin ulcer of diabetes mellitus and chronic kidney disease. They do not have to be “induced,” or genetically manipulated, to be pluripotent or be purposive cells before transplantation as required with some other cell varieties. They can be collected as cells positive for SSEA-3, a surface marker for pluripotent stem cells, from readily accessible sources such as the bone marrow (~0.03% of the total mononucleated cell population), and from cultured fibroblasts (several %), as well as from the dermis and adipose tissue. Recently, Muse cells are shown to circulate in peripheral blood in healthy donors, and the number increases in stroke patients in an acute phase, suggesting that endogenous Muse cells are mobilized into peripheral blood to repair tissues while their number is not sufficient to recover, and that supply of exogenous Muse cells is expected to deliver statistically meaningful functional recovery. Overall, Muse cells are a feasible source for cell-based approaches,and may safely provide clinically relevant regenerative effects compatible with the ‘body’s natural repair systems’ by simple cost-effective strategy-collection of Muse cells from sources, large scale expansion and intravenous injection.

 

  • 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: New York

Session Introduction

Simon Berkovich

The George Washington University, USA

Title: Nervous system as the producer of pinpoint energy for motions of living organisms

Time : 14:40-15:05

Speaker
Biography:

Simon Berkovich has completed his PhD from the USSR Academy of Sciences. He played a leading role in a number of advanced research and developmentprojects. He has several hundred professional publications in various areas of Physics, Electronics, Computer Science, and Biological Cybernetics. He is an author of six books and holds 30 patents. In 2002, he was elected as a member of the European Academy of Sciences "for an outstanding contribution to computer science and the development of fundamental computational algorithms". In 2014, he won the GWU Technology Transfer Innovation Competition, patent is pending.

Abstract:

This work explicates the physical basis of material motions in living systems. These sophisticated motions combine information control and mechanical actuation. Simplistic thinking sticks to a seemingly unyielding scheme: nervous
system sends control signals while the energy comes from the food. Obviously, such a trivial scheme imitates robots that efficiently employ artificial muscles. But how energy immediately appears in a given place and time in suitable quantities? Momentously, in our idea neural signals do not incite energy, but actually generates it from a new physical phenomenon due to neural pulses relocations. This elucidates the puzzling situation why nervous system utilizes moving excitations rather than simply sending electricity as through regular wiring. Actually, neuromorphic functionality is not decisive for biological information processing, as has been considered in our previous works. There, the origination of biological energy is referred to [13]: Law of inertia and the primal energy in the cellular automaton universe. This primal energy is a driving force for otherwise unclear property of inertia not to mention the incredible NASA EM drive. The incoming energy per second for one cellular automaton node is given by Plank’s constant E= hν; this energy influx sustains the rest mass clarifying the entire meaning of E=mc2. This “nuclear” energy is the same as the chemical energy from moving neural pulses, but the later is millions times smaller since electronic reconfigurations in neurons are much less extensive than corresponding nucleonic transformations in atomic structures. The presented discovery has broad practical consequences.

Speaker
Biography:

Lisa Oliver has completed her PhD at University of Paris 7. She is currently working in the group of Dr. François Vallette at the CRCINA, INSERM-University of Nantes. She has published more than 40 papers in reputed journals.

Abstract:

Glioblastoma multiforme is the most common brain cancer in adults. Radiotherapy is the most effective post-operative treatment for the patients even though gliomas are considered one of the most radio-resistant tumors. As a consequence there is rapid recurrence of the tumor probably due to the presence of cancer stem cells (CSC), which are radio-resistant. Indeed, the dying irradiated tumor bulk would activate caspase-dependent pathways causing the release of growth-promoting factors that would mobilize and recruit CSC. One of these pathways is the Ca2+-dependent phospholipase A2, the activation of which increases the synthesis and release of arachidonic acid from apoptotic cells and the consequent release of prostaglandin E2 (PGE2). We have evaluated the role of PGE2 in glioma radio-resistance. We used an in-vitro approach using 3D primary cultures derived from representative glioma patients. We show that irradiated glioma cells produced and released PGE2 in important quantities independently of the induction of cell death. We demonstrate that the addition of PGE2 enhances cell survival and proliferation though its ability to trans activate the Epithelial Growth Factor receptor (EGFR) and to activate β-catenin. Indeed, PGE2 can substitute for EGF to promote primary cultures survival and growth in vitro and the effect is likely to occur though the prostaglandin E2 receptor EP2.

Speaker
Biography:

Timothy A Blenkinsop has completed his PhD from New York University and Post-doctoral studies with Dr. Sally Temple at the Neural Stem Cell Institute. He is an Assistant Professor at Icahn School of Medicine at Mount Sinai, a leader in Stem Cell Research. He has published more than 20 papers in reputed journals which have been highlighted in Nature and Cell.

Abstract:

Retinal pigment epithelium is at the heart of many blinding diseases, including age-related macular degeneration, proliferative vitreoretinopathy and others. In early vertebrates, RPE are capable of regenerating the retina when damaged. In mammals, RPE have also shown regenerative capabilities, albeit at a reduced capacity. We have recently demonstrated adult human RPE exhibit regenerative capacity, including self-renewal properties and ability to differentiate into multiple lineages upon appropriate stimuli. We are exploiting state of the art sequencing technologies to understand both at the transcriptional and epigenetic levels what endows RPE with this regenerative capacity. We hypothesize the epigenetic flexibility naturally embodied by RPE allows their plasticity and as a result, confer regenerative potential. We are developing strategies to exploit this plasticity potential, and nudge RPE towards regenerative rather than pathological outcomes, with the final goal to develop therapies to restore lost retinal function.

Speaker
Biography:

Mladen-Roko Rasin has completed his MD and PhD from University of Zagreb and Post-doctoral studies from Yale University School of Medicine. He is an Associate Professor at Rutgers University. He has published more than 20 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Neural stem cell (NSC) differentiation requires precise spatiotemporal regulation during neurogenesis to generate a properly functioning central nervous system. This differentiation sequence is regulated by changes in gene expression (transcription) and protein synthesis (translation). Time-dependent gene transcription is thought to be a major regulator of  NSC differentiation, but time-dependent regulation of mRNA translation is also emerging as a key control mechanism. Indeed, we found that RNA binding proteins (RBP) control spatiotemporal mRNA translation events in neocortical neural stem cells in vivo and dictate production of distinct neuronal subtypes. Interestingly, roles of these RBPs are under the control of a timed neurotrophic factor. This is a novel molecular mechanism of post-transcriptional control during NSC differentiation in vivo. These findings may open new avenues for treating neurodevelopmental disorders associated with abnormal NSCs, mRNA translation, and/or central nervous system development and regeneration.

Biography:

Abstract:

Background: Mesenchymal stem cells (MSCs) are self-renewing cells that have extensive capacity for in vitro expansion with high yield and immunomodulatory effects, that's why they are excellent choice in regenerative medicine. However, clonal analysis of these cells has revealed that they are a heterogeneous mixture of cells. Therefore, clones derived from a single cell would provide a homogeneous population of MSCs and therapeutic efficacy of MSCs population may be enhanced by the use of selected multilineage clones.
Aim of the Work: Cloning of umbilical cord blood MSCs, by limiting dilution method, could provide a better source for MSCs with high stemness calibre to meet clinical demands.
Methodology: Isolation, expansion and cloning by limiting dilution method of human umbilical cord blood MSCs were done. Two cord blood samples, Mother (A) and Mother (B) were compared with their corresponding daughter clones regarding their proliferation efficiency, surface antigen expression, pluripotent and proliferation genes expression, as well as, their differentiation potentials. 
Results: MSCs were successfully isolated from two cord blood samples (Mother (A) and Mother (B)) and cloned by limiting dilution method to give 7 single clones for Mother (A) and 8 single clones for Mother (B). Mother (B) was fast growing, with higher PD and shorter PDT than Mother (A). It showed higher pluripotency and proliferation genes expression, as well as, a higher differentiation percent on the three mesodermal lineages level. The daughter clones (A2, A5) had a higher stemness criteria than their Mother (A) and other clones, whereas, Mother (B) showed a higher stemness characteristics than its daughter clones, except for clone B6 which showed comparable result to its mother. Conclusion: Cloning of MSCs to obtain homogeneous populations of cells with efficient proliferation and differentiation potentiality could be of significance for clinical applications. Moreover, this study draw the attention to the importance of CD105 as a possible selection marker for MSCs with better stemness properties, represented as higher proliferation efficiency and/or stronger differentiation potentiality.

Speaker
Biography:

Abstract:

Cirrhosis, the end result of long-term liver damage, places a significant burden on health care worldwide. Liver transplantation is the only definitive therapeutic option for these patients. However, the worldwide shortage of donor livers has prompted the search for alternative cell therapies. The prospective clinical use of autologous multipotent mesenchymal stem cells (MSCs) isolated from bone marrow (BM) holds enormous promise for the treatment of a large number of diseases which among them is end stage liver disease. Sixty patients with post-hepatitis C virus (HCV) end-stage liver disease were included in this study. They were randomized into two groups: Group 1: 35 patients to whom granulocyte colony-stimulating factor (G-CSF) was administered for 5 days to mobilize their hematopoietic stem cells. Following leukapheresis, CD34(+) stem cells were isolated, amplified, and partially differentiated in culture, then re-injected via peripheral-vein infusion. Group 2: 25 patients who received regular liver-supportive treatment only (control group). Hepatic fibrosis was assessed in Group I by detection of procollagen IIIC peptide level (PIIICP) and procollagen III N peptide level (PIIINP). Liver functions were markedly improved in 57.1% of patients in Group I. Significant changes were reported in albumin (P=0.000), bilirubin (P=0.002), increased international normalized ratio (INR) (P=0.017), prothrombin concentration (P=0.029) and alanine transaminase (ALT) levels (P=0.029), with stabilization of clinical and biochemical status in 14.3% of cases. While no significant improvement was detected in any patient in Group II. The pretreatment values of s-PIIICP and s-PIIINP were 8.2±3.7 and 395±175, respectively, with a decrease to 7.3±2.1 and 338±95, respectively, 3 months after MSC therapy, however, the difference was statistically nonsignificant (P=0.7). A significant correlation coefficient was reported after 3 months between the s-PIIINP and prothrombin concentration (P=-0.5) and between s-PIIICP and ascites (P=0.550). It can be concluded that a combination of G-CSF with MSCs will greatly improve the outcome of stem cell-treated patients with end-stage liver disease. In addition the peripheral intravenous infusion is an easy and convenient way of stem cells delivery, with less-invasive and less traumatic effects compared with intraarterial infusion route. Moreover, IV infusion of MSCs after G-CSF mobilization improves s-albumin within the first 2 weeks and prothrombin concentration and alanine transaminase after 1 month. Furthermore, MSCs may act directly through preventing collagen formation, as evidenced by their ability to reduce the hepatic fibrosis markers. Taken together, our data provides evidence that CD34(+) MSCs followed G CSF mobilization is excellent for liver stem cell therapy to retain liver mass and restore liver functions.

Shahin Rafii

Ansary Stem Cell Institute, USA

Title: Vascular niche signals in organotypic stem cell regeneration

Time : 17:30-17:55

Speaker
Biography:

Abstract:

Stem cell self-renewal and fate determination are dependent on niche-derived signals. However, the source of the niche cells and mechanism by which these signals regulate regeneration are not fully defined. Tissue-specific endothelial cells (ECs) by production of angiocrine factors establish an instructive vascular niche that choreographs stem cell homeostasis and organ regeneration. During development and regenerative processes, vascular niche cells oscillate the supply of (stimulatory)/(inhibitory) angiocrine factors and others are yet unknown factors. Theseangiocrine signals coordinate the self-renewal and differentiation of organotypic stem cells, such as hematopoietic stem cells (HSCs). To uncover the mechanism by which these angiocrine signals regulate stem cell reconstitution, we have devised an in-vivo tissue-specific vascular niche platform for expansion of HSCs and for generating vascularized cardiac, epithelial, hepatic and neural 3D organoids. Employing this vascular niche model, we show that ECs deploy signals that are essential for the specification, self-renewal and differentiation of human, mouse and non-human primate HSCs. Co-culture of adult marrow-derived hematopoietic cells with ECs results in 25 to 50 fold clonal HSC self-renewal with the capacity of long-term, multi-lineage engraftment in mice and non-human primate hosts. Vascular niche cells are also essential for pluripotent-independent conversion of readily accessible adult ECs into engraftable HSCs. To prove this point, we transduced human or mouse adult mature ECs with Runx1/Spi1/Gfi1/FosB transcription factors along with vascular niche-induction enabling step-wise conversion of these ECs into long-term repopulating immunocompetent HSCs. Clonal populations of converted HSCs expanded on vascular niche in-vitro, and fully reconstituted multi-lineage hematopoiesis in rodents. Co-infusion of the ECs along with HSCs augmented hematopoietic recovery, underscoring the significance of vascular niche-signals in stem cell reconstitution in-vivo. To translate the potential of vascular niche to the therapeutic setting, we have engineered generic ECs capable of vascularizing epithelial, hepatic, neural and cardiac 3D organoid cultures. Cross talk of ECs with tissue-specific stem cells promotes proper patterning and remodeling of these organoids into functional tissues. Using in-vivo regenerative models, we showed that transplantation of ECs stimulates hematopoietic, hepatic and lung repair without provoking maladapted fibrosis. These approaches have allowed us to uncover the molecular determinants of vascular heterogeneity; bringing us closer to translate the regenerative potential of ECs for organ repair to the clinic. Tissue-specific vascular-stem cell organoid cultures facilitate screening by gene-editing and small molecule libraries to identify unknown vascular niche signals that coordinate stem cell self-renewal and differentiation for functional organ repair.