Day 2 :
Keynote Forum
Michael D West
AgeX Therapeutics, USA
Keynote: Induced Tissue Regeneration (iTR): Leveraging the Unique Regenerative Potential of Pluripotent Stem Cell-Derived Therapeutics
Time : 09:00-09:30
Biography:
Dr. West is Co-Chief Executive Officer of BioTime, Inc. (NYSE MKT: BTX) and CEO of BioTime’s subsidiary AgeX Therapeutics, Inc. BioTime is focused on developing an array of research and therapeutic products using pluripotent stem cell technology. He received his Ph.D. from Baylor College of Medicine in 1989 concentrating on the biology of cellular aging. He was the founder and first CEO of Geron Corporation of Menlo Park, California (Nasdaq: GERN), held positions as CEO, President, and Chief Scientific Officer at Advanced Cell Technology, Inc., which was acquired by Astellas Pharma, Inc., and founded Asterias Biotherapeutics (NYSE MKT: AST).
Abstract:
Human pluripotent stem cell lines display the potential to cascade through all primary germ layers and hence, all human somatic cell types. This pluripotency has led to the prospect of using working cell banks of pluripotent cells to generate previously rare and valuable cell types on an industrial scale. The striking capacity of of pluripotent stem cells to form organoids in vitro, a property not typically seen in adult-derived cells, may reflect the unique regenerative potential of somatic cells before undergoing the embryonic-fetal transition (EFT). The demonstration that pre-EFT embryonic progenitors can be robustly clonally expanded is leading to a facile comparison of the transcriptomes of embryonic/regenerative cells and their adult counterparts. The identification of markers of EFT such as COX7A1 expression, opens the door to the deliniation of the molecular pathways regulating the biology of EFT with potentially profound implications for novel quality control assays useful in the manufacture of pluripotent cell-derived therapeutics, but perhaps more importantly, methods for inducing tissue regeneration in vivo, as well as new insights into cancer biology. Examples of the utility of this biology in the context of the manufacture of embryonic brown adipocyte and vascular progenitors, as well as well as in modulating iTR for therapeutic effects in age-related degenerative disease and cancer will be discussed.
Keynote Forum
Mark Berman
University of Southern California, USA
Keynote: Autologous Adipose Stromal Vascular Fraction – Lessons from 7 Years of Clinical Experience
Time : 9:30-10:00
Biography:
Mark practices cosmetic surgery and stem cell surgery in Beverly Hills. Together with Elliot Lander, they co-founded the California Stem Cell Treatment Center and then the Cell Surgical Network. He was the 2010 President of the American Academy of Cosmetic Surgery. His pioneering work in facial rejuvenation with autologous fat transfers led him into the arena of adipose stem cell investigations based upon a multidisciplinary approach to patient care.
Abstract:
Since 2010, I’ve been involved with investigative deployment of autologous adipose stromal vascular fraction (SVF) and more recently, autologous expanded mesenchymal cells (MSCs). During this time Elliot Lander, MD and I have established an international network (Cell Surgical Network) that teaches physician affiliates a simple surgical procedure to harvest adipose tissue and produce filtered SVF. No surgical procedure is “closed” however, the process is very safe, fairly simple, and outcomes analysis has been very satisfactory. Our clinical investigations have not only shed light on potential uses, we have increased our understanding of how cells can be most effective and where there have been some disconnects between the laboratory evaluation and the actual treatment of patients. We have also learned lessons about what drugs do and how our autologous stem cells are fundamentally different from drugs, in spite of the current FDA regulations. I will present information about our published safety paper, current data, and some unique areas of research in concussion, paralysis and unique deployment methods for some neurologoical diseases.
Keynote Forum
Esma S Yolcu
University of Louisville, USA
Keynote: Engineering bone marrow cells with an immunomodulatory protein for the prevention of graft-vs-host disease
Time : 10:00-10:30
Biography:
Esma S. Yolcu is Assistant Professor of Microbiology and Immunology and the Director of Imaging Facility at the Institute for Cellular Therapeutics and member of James Brown Cancer Center, University of Louisville, Louisville, KY. Dr. Yolcu received her Ph.D. degree from University of Ankara, Ankara, Turkey and joined the University Of Louisville School Of Medicine in Louisville, KY, to pursue her postdoctoral training. Dr. Yolcus research focuses on novel immunomodulatory approaches for the induction of tolerance to auto and alloantigens for the purpose of treating rejection and autoimmunty. Dr. Yolcu is the recipient of several awards, member of various national and international societies, serves on Editorial Board of scientific journals, and published over 67 peer-reviewed papers, abstracts, and review articles in high ranking journals, such as Immunity, Circulation, Blood, and the Journal of Immunology.
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.
Keynote Forum
Khalid Shah
Harvard Medical School, USA
Keynote: Receptor targeted engineered stem cells: Therapeutic application for cancer and beyond
Time : 10:30-11:00
Biography:
Khalid Shah is an Associate Professor at Harvard Medical School and the Director of the Center for Stem Cell Therapeutics and Imaging at Brigham and Women’s Hospital (BWH). He is also the Vice Chair of Research for the Department of Neurosurgery at BWH and a Principal Faculty at Harvard Stem Cell Institute in Boston. Since his move to BWH, he has started a joint Center of Excellence in Biomedicine with KACST and is also directing the new Center. He and his team have pioneered major developments in the stem cell therapy field, successfully developing experimental models to understand basic cancer biology and therapeutic stem cells for cancer, particularly brain tumors. These studies have been published in many high impact journals like Nature Neuroscience, PNAS, Nature Reviews Cancer, JNCI, Stem Cells and Lancet Oncology. Recently, his work has caught the attention in the public domain and as such it has been highlighted in the media world-wide including features on BBC and CNN. He holds current positions on numerous councils, advisory and Editorial Boards in the fields of stem cell therapy and oncology. In an effort to translate the exciting therapies developed in his laboratory into clinics, he has recently founded biotech company, AMASA Technologies Inc. whose main objective is the clinical translation of therapeutic stem cells in cancer patients.
Abstract:
Stem cell-based therapies are emerging as a promising strategy to tackle different disease types. We have identified different cell surface receptors on both tumor cells and tumor cell associated endothelial cells and engineered stem cells express bi-specific therapeutic agents that target these receptor types. Using our recently established invasive, recurrent and resection models of primary brain tumors (GBM) and breast and melanoma metastatic tumors in the brain that mimic clinical settings, we show that engineered human mesenchymal stem cells and neural stem cells expressing novel bi-functional proteins or loaded with oncolytic viruses target both the primary and the invasive tumor deposits and have profound anti-tumor effects. These studies demonstrate the strength of utilizing engineered stem cell based receptor targeted therapeutics for developing cancer therapeutics and have implications for developing innovative therapies for different diseases.
Keynote Forum
Magnus S Magnusson
University of Iceland, Iceland
Keynote: T-patterns and temporal and spatial self-similarity across many orders of maginitude: From proteins and neurons to only big-brain mass societies
Time : 11:20-11:50
Biography:
Magnus S. Magnusson, Research Professor, founder and director of the Human Behavior Laboratory University of Iceland. PhD in 1983, University of Copenhagen. Author of the T-pattern model and detection software THEMETM (PatternVision.com), focused on real-time organization of behavior. Co-directed DNA analysis. Numerous papers (>1700 citations) and talks/keynotes in ethology, neuroscience, mathematics, religion, proteomics and mass spectrometry. Deputy Director 1983-1988, in National Museum of Natural History, Paris. Repeatedly invited temporary Professor at the University of Paris, V, VIII and XIII. Since 1995, in collaboration between now 32 universities initiated at the University of Paris V, Sorbonne, based on “Magnusson’s analytical model”.
Abstract:
This talk may be seen as a message between areas with boundaries increasingly blurred. The ongoing work was initially inspired by the animal and human ethological (biology of behavior) research of Nico Tinbergen, Konrad Lorenz and Karl von Frish for which they shared a Nobel Prize in 1973, and by E. O. Wilson’s research on insect societies. The focus, however, soon turned to defining and detecting recurrent behavioral patterns exploiting the increasing computational possibilities given adequate pattern models and software. Developing both became the major task since the late 1970´s resulting around 1980 in a pattern type, named T-pattern and corresponding detection algorithms implemented as THEMETM (hbl.hi.is, patternvision.com). T-patterns are multicategorial, hierarchical and self-similar, recurring on a single dimension with statistically significant translational symmetry now abundantly detected in human and animal behavior and interactions (Casrrubea et al., comprehensive review 2015, Neuroscience Methods). When later applied to the neurons in neuronal netwroks in rats’ olfactory lobes (Nicol et al 2015), numerous complex T-patterns were found. Self-similarity of temporal patterning thus appeared on very different levels of biological organization. Consequently, the spatial structure of DNA and proteins has been explored suggesting much (striking) T-pattern organization. T-pattern related self-similarity over many orders of magnitude in biological spatial and dynamic structure thus seems to exist. It, moreover, seems to include striking self-similarity from Cell Cities (protein cities) to the only big-brain (i.e. human) mass-societies, critically based on evolving, durable and massively copied T-patterned strings of, respectively, molecular and alphabetic units, external to the citizens.
- Tissue engineering
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
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 development projects. 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. Th ese 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 artifi cial 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. Th is 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. Th ere, the origination of biological energy is referred to [13]: Law of inertia and the primal energy in the cellular automaton universe. Th is primal energy is a driving force for otherwise unclear property of inertia not to mention the incredible NASA EM drive. Th e incoming energy per second for one cellular automaton node is given by Plank’s constant E= hν; this energy infl ux sustains the rest mass clarifying the entire meaning of E=mc2. Th is “nuclear” energy is the same as the chemical energy from moving neural pulses, but the later is millions times smaller since electronic reconfi gurations in neurons are much less extensive than corresponding nucleonic transformations in atomic structures. Th e presented discovery has broad practical consequences.
- 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
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.
Lisa Oliver
University of Nantes, France
Title: Radiation-induced PGE2 sustains glioma cell growth and survival through EGF signaling
Time : 15:05-15:30
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.
Timothy A Blenkinsop
Icahn School of Medicine at Mount Sinai, USA
Title: Examining adult human retinal pigmented epithelium plasticity for developing regenerative therapies
Time : 15:30-15:55
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.
Mladen-Roko Rasin
Rutgers University, USA
Title: Timed post-transcriptional events in neural stem cells determine their output
Time : 16:15-16:40
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.
Shereen Shawky
Cairo University, Egypt
Title: Isolation and characterization of human cord blood mesenchymal stem cells multipotent clones
Time : 16:40-17:05
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.
Ayman Salah
Cairo University, Egypt
Title: The merits of autologous mesenchymal stem cells peripheral vein infusion in patients suffering from end stage liver cirrhosis
Time : 17:05-17:30
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
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.
- Stem Cell Therapy | Tissue Engineering | Tumour Cell Science | Stem Cells | Regeneration and Therapeutics | Stem Cell Niches | Diseases and Stem Cell Treatment
Location: New York
Session Introduction
Helen McGettrick
University of Birmingham, UK
Title: Podoplanin regulates mesenchymal stem cell behaviour in flowing blood and within the tissue
Time : 11:50-12:15
Biography:
Helen McGettrick has completed her PhD in 2006, followed by three Post-doctoral research positions at the University of Birmingham (UK). She was appointed as a University Fellow in Inflammation Biology in 2011, and a year later 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 currently a Senior Research Fellow at the University of Birmingham and an Honorary Lecturer at the University of Glasgow and Newcastle University (UK). She has ~40 published articles with ≈ 760 citations, has filed three patents and received funding from Wellcome Trust, Medical Research Council UK, Pfizer and British Heart Foundation.
Abstract:
Mesenchymal stem cells (MSC) are tissue resident stromal cells with immunomodulatory properties which are increasing used therapeutically via injection into the blood. Within the blood and tissue, their adhesive and migration properties, along with their interactions with other blood cells may influence their fate. Human bone marrow (BM) or umbilical cord (UC) MSC adhered from flow to matrix proteins. However, they displayed distinct interactions with platelets when perfused in whole blood, with only UCMSC inducing platelet aggregation and causing a marked drop in platelet count when infused systematically into mice. UCMSC, but not BMMSC, expressed a mucin-like protein called podoplanin, which is known to bind to CLEC-2 expressed on platelets. Expression of podoplanin varied in UCMSC donors; most were positive, but some donors lacked expression (podoplanin negative). Only podoplanin-positive UCMSC were able to aggregate platelets in vitro and in vivo, and this could be blocked by competitive inhibition with recombinant CLEC-2. Human UCMSC caused reduction of platelet count when mixed with mouse blood, but the response was lost with blood taken from mice deficient in CLEC-2. Separately we observed that podoplanin expression enhanced UCMSC migration in vitro in a Rac-1 dependent manner. Thus, the origins of MSC and their expression of podoplanin may have impact on their behavior in blood and tissue. During therapy, MSC interactions with platelets could be thrombotic, but might also promote targeting of MSC to damaged tissue, where they could exert their reparative and immunomodulatory effects.
G Ian Gallicano
Georgetown University Medical Center, USA
Title: CRISPR/CAS9 ablation of individual miRNAs from a miRNA family reveals their individual efficacies for regulating cardiac differentiation
Time : 12:15-12:40
Biography:
G Ian Gallicano has completed his PhD in 1994 from Arizona State University afterwhich he has completed his Post-doctoral studies at The University of Chicago/Howard Hughes Institute. He has been the Director of the Transgenic Shared Resource at the Lombardi Comprehensive Cancer Center and is currently implementing CRISPR gene editing technology at GUMC. He has published more than 60 papers in reputed journals and is currently an Editorial Board Member for the journal Stem Cells as well as the Editor-in-Chief for American Journal of Stem Cells.
Abstract:
MicroRNAs are quickly entering the causal fray of developmental defects. These small, non-coding RNAs use a 7-8 basepair seed sequence to target a corresponding sequence on one or multiple mRNAs resulting in rapid down-regulation of translation. miRNAs can also control protein amounts in cells. As a result, if miRNAs are over or under expressed during development protein homeostasis can be compromised resulting in defects in the development of organ systems. Here, we show that during differentiation of embryonic stem cells, individual miRNAs that reside in the miRNA17 family (composed of 15 miRNAs) do not share the same function even though they have the same seed sequence. The advent of CRISPR/CAS9 technology has not only yielded a true observation of individual miRNA function, it has also reconnected advanced molecular biology approaches to classical cell biology approaches such as gene rescue. We show that miRNA106a and to a lesser extent miR17 and 93 target the cardiac suppressor gene Fog2, which specifically suppress Gata-4 and Coup-TF2. However, when each miRNA is knocked out, we find that their targeting efficacies for Fog2 differ resulting in varying degrees of cardiac differentiation.
Adalberto L Rosa
University of Sao Paulo, Brazil
Title: Cell therapy strategy for enhancing bone repair
Time : 12:40-13:05
Biography:
Adalberto L Rosa, DDS, MSc, PhD, is working as a full Professor of Oral and Maxillofacial Surgery in the University of São Paulo, Brazil. He has been developing research projects focused on Tissue Engineering and Cell Therapy aiming at bone repair using either in vitro or in vivo models.
Abstract:
Cell therapy has been investigated as a promising treatment for bone defects in situations where the trauma extension surpasses the bone regenerative capacity. In this scenario, the aim of our study was to evaluate the effect of mesenchymal stem cells (MSCs) and osteoblasts (OBs) on bone repair. Bone marrow MSCs were harvested from rat femurs, selected by adherence to polystyrene and characterized by the expression of a panel of surface markers. OBs were differentiated from these MSCs by culturing them in osteogenic medium and characterized by the gene expression of bone markers. Defects with 5-mm diameter were created in rat calvarias and after 2 weeks they received a direct injection of: (1) MSCs, (2) OBs (5*106 cells in 50 μL of PBS for each cell type) or (3) PBS without cells (control). Bone formation was evaluated 4 weeks post-injection by microtomographic and morphometric analyses. The data were compared by ANOVA (n=12, p≤30.05). MSCs presented a high percentage of cells expressing CD29 and CD90 and a low percentage expressing CD31, CD34, CD44 and CD45. OBs displayed higher gene expression of ALP, OC and OPN. Luciferase-expressing MSCs and OBs were detected within the defects till 12 days post-injections. The 3-D microtomography reconstructions as well as morphometric parameters showed more bone formation in defects injected with cells compared with control. Bone volume (p=0.03), % bone volume (p=0.03) and trabecular number (p=0.05) were higher in cell-injected defects, trabecular separation (p=0.002) was lower while bone surface (p=0.07) and trabecular thickness (p=0.4) were not affected by treatments. There was no difference between MSCs and OBs-injected defects in any of the evaluated parameters. The results show that the treatment of calvarial defects with cells irrespective of the differentiation stage increased bone repair suggesting that cell therapy is a potential strategy to induce bone regeneration in challenging clinical conditions.
Sean Berman
Cell Surgical Network, USA
Title: The treatment of traumatic brain injury and chronic traumatic encephalopathy in a rat model with stromal vascular fraction and expanded adipose derived mesenchymal stem cells
Time : 13:55-14:20
Biography:
Sean Berman has completed his BS at Amherst College and his MS at Louisiana Tech University. As a college quarterback, he saw first hand effects of traumatic brain injury and realized the clear lack of active treatment options avaiable. He has been researching brain injuries and stem cells in the laboratory setting for 5
years now and actively collaborates with physicians in the hopes of developing clinically relavent reserach, findings and solutions.
Abstract:
Traumatic brian injury results after a blow to the head induces a terminal change in velocity causing the brain to be displaced beyond the blood brain barrier. This impact causes a cascade of cellular injuries. The initial injury is vascular and effects neuronal cells as well. The secondary injury is autoimmune in nature. Adipose derived mesenchymal stem cells (ADSCs) have the ability to migrate to sites of injury (inflammation) and repair damaged neuro-vascular tissue. They also can mitigate immune responses due to their immuno-modulatory characteristics. The first part of our study examined the use of fresh stromal vascular fraction (SVF), which contians ADSCs and hematopoetic stem cells (HSCs), delivered via tail vein injection, to mitigate the effects of shockwave induced TBI. The administration of SVF imporved both memory and motor skills functions. Another model was developed to model chronic traumatic encephalopathy (CTE) in the rat model. In this follow up study, rats received a shockwave induced TBI once a week for 10 weeks, followed by 1 million culture expanded ADSCs via tail vein injection (saline control). The rats were monitored for memory and motor skills. Histology was performed and showed human nucleated cells homed in on the site of injury and developed into functional tissue. These two studies show that cell treatmnet improves patient with acute brain injury and can prevent otehrwise long term expected side-effects of CTE.
MinYoung Kim
CHA University, Republic of Korea
Title: Umbilical cord blood cell therapy for children with cerebral palsy
Time : 14:20-14:45
Biography:
MinYoung Kim is currently working as Professor and Director of Department of Rehabilitation Medicine and Rehabilitation and Regeneration Research Center,
CHA University, Korea. She graduated from Yonsei University College of Medicine, Seoul, Korea in 1991. She obtained her Doctor of Medical Science degree in 2002 and worked as a Post-doc for UCSanDiego in 2007-2008. She has been served as a Senior Editor of American Journal of Stem Cell, and Associate Editor of Restorative Neurology and Neuroscience. She published more than 34 articles of SCI and PubMed journals during past 7 years. Her fields of research interest are "application of stem cells for brain disease" and "brain rehabilitation".
Abstract:
Umbilical cord blood (UCB) cells have been suggested to exert therapeutic effect for cerebral palsy (CP). By conducting double-blind randomized controlled trials, we could observe the safety and efficacy of allogeneic UCB infusion in CP subjects. Physical and mental function evaluations using standardized measures including Gross Motor Performance Measure, Gross Motor Function Measure, and Bayley Scales of Infant Development-II Mental and Motor scales, and muscle strengths of extremities, showed therapeutic efficacy of UCB cells. To assess therapeutic mechanism of UCB in CP, 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) and diffusion tensor images were also used. 18F-FDG-PET/CT showed activation of basal ganglia and thalami and anti-inflammatory findings in periventricular white matter after UCB administration. Diffusion tensor images suggested improvement in white matter integrity which correlated with motor performance. According to molecular works using blood samples of the CP subjects, we found possible role of innate immune response triggered by UCB infusion. Elevations of pentraxin 3 and interleukin-8 levels in plasma and toll-like receptor 4 expression in blood cells were observed up to 12 days after UCB treatment and those correlated with the motor improvements observed up to 6-month post-injection.
Nassim Abi Chahine
ACE Cells Lab. Ltd, UK
Title: The regentime technique in stem cell therapy, a gate to immortality
Time : 14:45-15:10
Biography:
Abstract:
As people are living longer, they are more likely to acquire chronic diseases or develop age-related conditions. Globally, there is an increasing incidence of chronic and degenerative diseases. In Helsinki Declaration, the innovative therapy has a sacred place in the advancement of medicine, and the role of the scientist diffusing the good information has been blessed since days of Hippocrates. Since the first decade of the 21st century, a widespread group of stem cell scientists lead a marvelous innovation in medicine, but also a tough confrontation with some sides. We aim to show the good of this new sector and that our work has its transparent purpose; to accelerate the process of knowledge about regeneration. Looking for a more satisfying solution at all medical levels, we developed at ACE Cells Lab the Regentime® procedure which is based on the transplantation of proliferated partially differentiated and specifically redirected autologous adult bone marrow derived mononuclear progenitor stem cells. After 9 years of devotion for regenerative medicine based on technique development, academic lecturing, and conferencing, we tend today to emphasize the importance of stem cells as a biological noble tool in our war against diseases.This presentation is reviewing, discussing, and analyzing the latest in stem cells field, all into a homogenous corpus serving the new generation of medics, enlightening the way for a better health. At the end, we will expose results of different research therapies in a realistic figure facilitating to physicians the act of choosing the best stem cell therapeutic methods, making the expected result clearer.
Nadja Zeltner
University of Georgia, USA
Title: Modeling disease of the peripheral nervous system
Time : 15:10-15:35
Biography:
Nadja Zeltner has received her PhD from Ichan School of Medicine at Mount Sinai in New York and has completed her Post-doctoral studies from Dr. Lorenz
Studer’s laboratory at Memorial Sloan Kettering Cancer Center in New York. Her research focuses on disease modeling using human pluripotent stem cells with particular focus on the peripheral nervous system (PNS). Her ultimate goal is employing this technology to further understand PNS disorders that will lead to the development of novel drugs and therapeutics. She has started her own research group at the Center of Molecular Medicine at the University of Georgia
Abstract:
Functional and molecular aspects of human genetic disease can be recapitulated in vitro using patient-specific pluripotent stem cells (PSCs). Familial Dysautonomia (FD) is a debilitating developmental and degenerative disorder that primarily affects derivatives of the neural crest (NC), such as the peripheral nervous system (PNS). For unknown reasons, FD patients present with mild or severe disease despite carrying the identical, homozygous point mutation in IKBKAP. We present in vitro phenotypes at various stages of development that capture severe and mild FD in human PSC-derived cellular lineages. Patient-specific cells only from severe but not mild FD display an impaired capacity of developing into NC derivatives, such as autonomic and sensory neurons, thus they have neurodevelopmental defects. Interestingly, however, both severe and mild FD cells show defects in peripheral neuron survival, indicating neurodegeneration as the primary culprit in mild FD. Importantly, we found that neuronal degeneration in mild FD can be halted by treatment with candidate therapeutic compounds kinetin and SKF-86466. Genetic rescue of the FD mutation in severe FD iPSCs reversed NC, but not sensory neuron lineage phenotypes, implicating that the known FD mutation does not account for all symptoms. Employing whole-exome sequencing (WES), we identified candidate mutations that were only found in severe but not mild FD patients, providing evidence that FD may constitute two genetic sub-diseases. Our study demonstrates that human PSC-based disease modeling is sensitive in recapitulating disease severity and paves the road for applications in personalized medicine. Using a chemical screen, we identified a compound that could rescue severe FD defects. This further paves the way towards future treatments tailored more specifically towards individual patients.
Diana Anderson
University of Bradford, UK
Title: Silver nanoparticle-mediated cellular responses in isolated Sertoli cells in vitro
Time : 15:35-16:00
Biography:
Diana Anderson has completed her PhD from the University of Manchester, UK in the Faculty of Medicine. She is the Established Chair in Biomedical Sciences at the University of Bradford. She has published more than 450 papers and 9 books, successfuly supervised 32 PhD studnets, has an Hirsch factor of 55. She is Editor-in-Chief of a Book series for the Royal Society of Chemistry and is a Consultant to many internaitional organisations, such as the World Health Organisation/International Programme of Chemical Safety. She is/has been Member of the Editorial Board of 10 international journals.
Abstract:
Exposure to silver nanoparticles (AgNPs) has been reported to be related to male reproductive toxicity in mammalian studies. The present study explored the mechanism of cytotoxic and genotoxic effects of AgNPs on a primary culture of mouse Sertoli cells in vitro. DNA damage was evaluated in the Comet assay; apoptotic cells were detected using terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labelling (TUNEL) assay and apoptosis markers such as p53 and bcl-2 and antioxidant enzymes such as catalase (CAT), glutathione peroxidase 1 (GPX-1) and superoxide dismutase 1 (SOD-1) were quantified using qPCR. The superoxide anion was detected using the nitroblue tetrazolium NBT reduction assay. Our study indicates that AgNP exposure causes increased oxidative stress levels, the activation of p53, repression of bcl-2 and reduction of endogenous antioxidant enzymes which are involved in the mechanistic pathways of AgNPs-induced DNA damage in the Sertoli cells in vitro. This may lead to reduced numbers of Sertoli cells through promoting early spermatogonial stem cell differentiation.
Kitai Kim
Weill Medical College of Cornell University, USA
Title: ZSCAN10 expression corrects the genomic instability of iPSC from aged donors by controlling redox status
Time : 16:20-16:45
Biography:
Kitai Kim has completed his PhD from the Univerity of Wisconsin at Madison, and Post-doctoral studies from Childrens Hospital Boston, Harvard Medical School. He is a faculty of the Memorial Sloan-Kettering Cancer Center, affiliated with Weill Medical College of Cornell University. He has reported major publications in stem cell field including histocompatible parthenogenetic ES cells, tissue-specific epigenetic memory of iPS cells, and biological significance of redox control by ZSCAN10.
Abstract:
Induced pluripotent stem cells (iPSC) can be used to produce transplantable tissues. However, iPSC generated from aged donors (A-iPSC) exhibit higher genomic instability, defects in apoptosis, and a blunted DNA damage response compared to iPSC generated from younger donors (Y-iPSC). We defined the underlying mechanism as a homeostatic imbalance between reactive oxygen species (ROS) and glutathione (a ROS scavenging metabolite). Excessive glutathione activity can blunt the normal DNA damage response signalling pathway, allowing cells with genomic mutations to persist that otherwise would have been eliminated by apoptosis. We found that the pluripotent specific factor, ZSCAN10, was poorly expressed in A-iPSC, and ZSCAN10 expression allows the establishment of A-iPSC without the negative effects of aging. We found that A-iPSC have a higher level of glutathione due to excessive expression of glutathione synthetase (GSS), which causes an imbalance of ROS and glutathione. ZSCAN10 directly binds the GSS promoter to suppress GSS expression. We also found that ZSCAN10 not only controls GSS expression (to determine the total quantity of glutathione) but also glutathione peroxidase (GPX2), which suppresses the excessive catalytic activity of glutathione by controlling its transition from an oxidized inactive form to a reduced active form. We found that GPX2 is controlled by the exosome-mediated RNA degradation pathway and that ZSCAN10 expression induces RNA exosome complex expression. We found the third mechanism that ZSCAN10 controls activity of pluripotent stem cell-specific glucose transporter 3 (GLUT3) and facilitates a shift in carbon source metabolism that suppresses oxidative phosphorylation and limits ROS production, consequently providing a selective advantage for cells with elevated glutathione during reprogramming to maintain the ROS-glutathione balance. Correcting the genomic instability of A-iPSC may particularly benefit older patients who are more likely to suffer from degenerative diseases with safer transplantable tissues.
Xiufeng Zhong
Sun Yat-sen University, China
Title: hiPSC-photoreceptors mimic human photoreceptor development in vivo
Time : 16:45-17:05
Biography:
Xiufeng Zhong is a Professor and PI at Zhongshan Ophthalmic Center, Sun Yat-Sen University, China. She received her MD from Nanchang University and PhD
degree in Ophthalmology from SYSU, and did Post-doc research at Johns Hopkins University School of Medicine. Her study for the first time demonstrates that hiPSCs can generate functional retina with light-sensing photoreceptors in vitro, holding a huge promise for blindness. She has published 60 peer-reviewed papers, 8 patents. Her research has got man.
Abstract:
Human induced pluripotent stem cells (hiPSC) have been proven to be able to generate retinal photoreceptors responsible for sight. However, it is still unclear how closely the derivatives of hiPSC mimic the naive cells so far. Thus, this study is to see whether hiPSC-derived photoreceptors recapitulate the development of human photoreceptors in vivo. hiPSC lines from different somatic source were used in this study. Cells were cultured on MatriGel with mTeSRTM1 medium. The procedure for inducing differentiation of hiPSCs toward a photoreceptor fate was based on a previously described protocol. Differentiating human iPSCs were followed by morphological observation and characterized by immunocytochemistry and RT-PCR with molecular markers of pluripotency and/or specific for different stages of photoreceptors. Under specific differentiation conditions and multi-step induction, hiPS cells gradually acquired expression of molecular markers characteristic of different stages of photoreceptors, including cones and rods. More interesting, rods and cones situated in the outermost layer of the retinal cups, forming outer nuclear layer like in vivo counterpart. TEM showed hiPS-derived PRCs developed not only inner segments but also outer segments—a key functional structure. The timeframe for acquisition of photoreceptor was very close to that of human photoreceptor embryogenesis. Our results provide strong evidence that derivatives of hiPSCs are capable of recapitulating the molecular and cellular features of human photoreceptor differentiation in vivo. This success provides a powerful model for the study of human photoreceptor development and opens up important possibilities for disease modeling and cell therapy.
Heidi Abrahamse
University of Johannesburg, South Africa
Title: Photobiomodulation and photobio-inhibition of cancer stem cells and use of photodynamic therapy as possible therapeutic modality
Time : 17:05-17:30
Biography:
Heidi Abrahamse is the Director of the Laser Research Centre, University of Johannesburg and Department of Science and Technology/National Research FoundationmSARChI Chair for Laser Applications in Health. Her research interests include, Photobiology and Photochemistry with specific reference to photodynamic cancer therapy, stem cell differentiation and wound healing. She has supervised 40 Master’s; 15 Doctorates and 12 Post-Doctorate fellows and has published 116 accredited journal publications, 42 full paper proceedings and 11 chapters. She serves on the Editorial Boards of 8 international journals while acting as reviewer for over 40 journals. She serves as Co-Editor in Chief of the international accredited journal Photomedicine and Laser Surgery.
Abstract:
Cancer is a global burden, which have prompted extensive research into cancer prevention and treatment for many decades. Scientific studies have shown that a subset of cells within a tumour, called cancer stem cells (CSCs), can initiate tumour genesis. Low-intensity laser irradiation (LILI) has been applied in the treatment of numerous diseases and pathological conditions. Photobiomodulation has been shown to stimulate proliferation of cells, capillary growth, and cellular metabolism as observed by adenosine triphosphate activation. It has been shown, by using different fluences and wavelengths, LILI, can either stimulate or inhibit cellular functions. Cancer research is highly focused on improving current cancer treatments. One method of targeted cancer therapy is Photodynamic therapy (PDT), LILI, along with a photochemical compound, is used. When implementing a mechanism by which CSCs are targeted, LILI might pose as a viable treatment option. Studies have shown that using high fluences of LILI cell death may be induced in normal and neoplastic cells. In our work, lung and breast CSCs were isolated using stem cell markers and irradiated at wavelengths of 636, 825 and 1060 nm at fluences ranging from 5 J/cm2 to 40 J/cm2. Post irradiation biochemical assays were conducted to monitor cellular responses including; proliferation and cytotoxicity, after 24 hours incubation. Results indicate that LILI, when treating CSCs, can induce either a bio-stimulatory or bio-inhibitory effect depending on the wavelength and fluence used. This study indicated successful cell damage in CSCs when using HF-LILI, as well as, stimulation of ATP production, when using lower fluences of LILI.
- Stem Cell Therapy | Tissue Engineering | Tumour Cell Science | Stem Cells | Regeneration and Therapeutics | Stem Cell Niches | Diseases And Stem Cell Treatment
Location: New York
Session Introduction
Joel I Osorio
Westhill University School of Medicine, Mexico
Title: RegenerAge System: Therapeutic effects of combinatorial biologics (mRNA and Allogenic MSCs) with a spinal cord stimulation system on a patient with spinal cord section
Time : 10:35-11:00
Biography:
Joel I Osorio is the CEO and Founder of Biotechnology and Regenerative Medicine at RegenerAge International ™ HYPERLINK "http://www.regenerage.clinic/"h(HYPERLINK"http://www.regenerage.clinic/" h www.regenerage.clinic). He is the Vice President of International Clinical Development for Bioquark, Inc. (HYPERLINK"http://www.bioquark.com/" h www.bioquark.comHYPERLINK "http://www.bioquark.com/" h ) and Chief Clinical Officer at ReAnima™ Advanced Biosciences(HYPERLINK "http://www.reanima.tech/" h www.reanima.tech) and Westhill University School of Medicine. Mexico. He pursued Advance Fellow by the American Board of Anti-Aging and Regenerative Medicine (A4M) and Visiting Scholar at University of North Carolina
Abstract:
As it has been previously demonstrated that coelectroporation of Xenopus laevis frog oocytes with normal cells and cancerous cell lines induces the expression of pluripotency markers and in experimental murine model studies that mRNA extract (Bioquantine® purified from intra and extra-oocyte liquid phases of electroporated oocytes) showed potential as a treatment for a wide range of conditions as Squint, Spinal Cord Injury (SCI) and Cerebral Palsy among others. The current study observed beneficial changes with Bioquantine® administration in a patient with a severe SCI. Pluripotent stem cells have therapeutic and regenerative potential in clinical situations CNS disorders even cancer. One method of reprogramming somatic cells into pluripotent stem cells is to expose them to extracts prepared from Xenopus laevis oocytes. We showed previously that coelectroporation of Xenopus laevis frog oocytes; with normal cells and cancerous cells lines, induces expression of markers of pluripotency. We also observed therapeutic effects of treatment with a purified extract (Bioquantine) of intra and extra-oocyte liquid phases derived from electroporated X. laevis oocytes, on experimentally induced pathologies including murine models of melanoma, traumatic brain injury and experimental skin wrinkling induced by squalene mono-hydroperoxide. The positive human findings for spinal cord injury and cerebral palsy with the results from previous animal studies with experimental models of traumatic brain injury, respectively. Because of ethical reasons, legal restrictions and a limited number of patients, we were able to treat only a very small number of patients. These results indicate that Bioquantine® may be safe and well tolerated for use in humans and deserves further study in a range of degenerative disorders. We propose that the mechanism of action of Bioquantine® in these various diseases derives from its unique pharmacology and combinatorial reprogramming properties.
In conclusion, these preliminary findings suggest that Bioquantine is safe and well tolerated on patients with cerebral palsy and spinal cord injury, among others. In addition to the regenerative therapy and due to the patient condition, we decided to include the RestoreSensor SureScan. Based on the electrical stimulation for rehabilitation and regeneration after spinal cord injury published by Hamid and MacEwan, we designed an improved delivery method for the in-situ application of MSCs and Bioquantine® in combination with the RestoreSensor® SureScan®. To the present day the patient who suffered a total section of spinal cord at T12-L1 shows an improvement in sensitivity, strength in striated muscle and smooth muscle connection, 11 months after the first therapy of cell regeneration and 3 months after the placement of RestoreSensor® at the level of the lesion, the patient with a complete medullary section shows an evident improvement on his therapy of physical rehabilitation on crawling from front to back by himself and standing on his feet for the first time and showing a progressively important functionality on the gluteal and legs sensitivity.
Purwati Sumorejo
Airlangga University, Indonesia
Title: The role of adipose derived mesenchymal stem cells as a treatment in autoimmune disease
Biography:
Purwati Sumorejo has finished her General Practition from Airlangga University in 1997. She has completed her studies in Internal Medicine. She is a Specialist(2008) from Airlangga University and also pursued her Doctoral program in Airlangga University from 2010-2012. Her research interest is in stem cell field. Since 2008, she is a Secretary of Stem cell Laboratory of Airlangga University and also Secretary of Surabaya Regenerative Medicine Centre. From 2015, she holdsa position of Chairman of Stem Cell Research and Development Centre Airlangga University, Surabaya, Indonesia. She has almost 60 publications in journals, papers and seminars.
Abstract:
Autoimmune diseases (ADs) are the third most common disease in United States affecting 5 to 8% of population. The major treatment of ADs is immunosuppressive drugs but these are not effective and associated with substantial toxicities. Adipose tissue is one of the most potent and concentrated source of mesenchymal stem cells (MSCs) as an anti-inflammatory and tissue protecting agent which will promote healing and also minimal invasive. This study is conducted in 20 patients with autoimmune diseases in various ages between 22 to 70 years old. Patients were treated with autologous adipose-derived MSCs transplantation through catheterization. The laboratory analysis result of patients before and after MSCs application in 6 months were measured which include haemoglobin (Hb), white blood cells (WBC), erythrocyte sedimentation rate (ESR), protein and blood levels in urine, high sensitivity c-reactive protein (hsCRP), C3 and C4 complement, anti-nuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA). MSCs are able to improve the performance of hemoglobin as shown in Hb which showed statistically significant increase (p=0.002). MSCs are able to reduce the inflammatory as shown in the number of leukocytes (p=0.015) and ESR (p=0.031) which showed statistically significant decrease. MSCs can repair the renal function with no presences of protein and blood in patient’s urine. MSCs are also able to augment the immune response as shown in hsCRP which statistically significant decrease (p≤0.001), while C3 and C4 complements statistically significant increase (p≤0.001). ANA and anti-dsDNA showed a negative result which means MSCs therapy may give a good response to heal the ADs.
Purwati Sumorejo
Airlangga University, Indonesia
Title: The role of adipose derived mesenchymal stem cells as a treatment in autoimmune disease
Time : 11:20-11:45
Biography:
Purwati Sumorejo has finished her General Practition from Airlangga University in 1997. She has completed her studies in Internal Medicine. She is a Specialist (2008) from Airlangga University and also pursued her Doctoral program in Airlangga University from 2010-2012. Her research interest is in stem cell field. Since 2008, she is a Secretary of Stem cell Laboratory of Airlangga University and also Secretary of Surabaya Regenerative Medicine Centre. From 2015, she holdsa position of Chairman of Stem Cell Research and Development Centre Airlangga University, Surabaya, Indonesia. She has almost 60 publications in journals,papers and seminars.
Abstract:
Autoimmune diseases (ADs) are the third most common disease in United States affecting 5 to 8% of population. The major treatment of ADs is immunosuppressive drugs but these are not effective and associated with substantial toxicities. Adipose tissue is one of the most potent and concentrated source of mesenchymal stem cells (MSCs) as an anti-inflammatory and tissue protecting agent which will promote healing and also minimal invasive. This study is conducted in 20 patients with autoimmune diseases in various ages between 22 to 70 years old. Patients were treated with autologous adipose-derived MSCs transplantation through catheterization. The laboratory analysis result of patients before and after MSCs application in 6 months were measured which include haemoglobin (Hb), white blood cells (WBC), erythrocyte sedimentation rate (ESR), protein and blood levels in urine, high sensitivity c-reactive protein (hsCRP), C3 and C4 complement, anti-nuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA). MSCs are able to improve the performance of hemoglobin as shown in Hb which showed statistically significant increase (p=0.002). MSCs are able to reduce the inflammatory as shown in the number of leukocytes (p=0.015) and ESR (p=0.031) which showed statistically significant decrease. MSCs can repair the renal function with no presences of protein and blood in patient’s urine. MSCs are also able to augment the immune response as shown in hsCRP which statistically significant decrease (p≤0.001), while C3 and C4 complements statistically significant increase (p≤0.001). ANA and anti-dsDNA showed a negative result which means MSCs therapy may give a good response to heal the ADs.
Haval Shirwan
University of Louisville, USA
Title: Pancreatic islets engineered with a chimeric PD-L1 protein overcome rejection in allogeneic recipients
Time : 11:45-12:10
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 Post-doctoral 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, 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:
Allogenic islet transplantation is an important therapeutic approach for the treatment of type 1 diabetes (T1D). However, graft rejection initiated and perpetuated by pathogenic T effector (Teff) cells presents a major barrier. One approach that has proven successful for promoting graft tolerance is shifting the T cell balance away from the induction of pathogenic Teff cells and towards the generation of protective T regulatory (Treg) cells. PD-1/PD-L1 immune checkpoint pathway plays an important role in the Teff and Treg balance with demonstrated clinical efficacy in cancer immunotherapy. We generated a chimeric PD-L1 molecule that can be transiently displayed on the surface of pancreatic islets. In vitro, PD-L1 enhanced TGF-beta-induced conversion of Teff into Treg cells and effectively suppressed the proliferation of Teff cells in response to alloantigen stimulation. In vivo, PD-L1-engineered BALB/c islet grafts under a short window of rapamycin treatment achieved sustained long-term graft survival and function. These results provide strong proof-of-efficacy and feasibility for using PD-L1 protein as an immunomodulator to promote allogeneic islet graft survival in the absence of continued immunosuppression.
Zita M Jessop
Swansea University Medical School, UK
Title: Isolation and characterization of human nasoseptal cartilage derived stem/ progenitor cells (CSPCs) for cartilage biofabrication
Time : 12:10-12:35
Biography:
Zita M Jessop is an Academic Clinical Lecturer in the Reconstructive Surgery and Regenerative Medicine Research Group at Swansea University and Registrar at the Welsh Centre for Burns and Plastic Surgery. After completion of Medicine at Cambridge University, she undertook surgical training in London Deanery before joining the Welsh Clinical Academic Training Pathway. Her Doctoral research is focusing on cartilage 3D bioprinting, has won significant awards from the Royal College of Surgeons of England, the British Association of Plastic, Reconstructive and Aesthetic Surgeons and the Medical Research Council. She is currently a Fulbrigth Scholar at the Wyss Institute, Harvard University.
Abstract:
Contemporary cartilage tissue engineered implants, many using unrelated adult stem cell sources do not produce stable, physiologically relevant cartilage. Although lacking intrinsic reparative ability, cartilage has been shown to contain a population of stem cells or progenitor cells, similar to other adult tissues, that are thought to be involved in maintenance of tissue homeostasis. Since they were first identified in articular cartilage, these so-called cartilage-derived stem/progenitor cells (CSPCs) have become the latest addition to the potential cell repertoire for cartilage tissue engineering. Unlike articular CSPCs, nasoseptal CSPCs have not been well studied, with definitive markers and molecular identity remaining obscure to date. We isolated human nasoseptal CSPCs using differential adhesion to fibronectin and undertook functional, genetic and immunophenotypic characterization using ac combination of RT-PCR, PCR array, Immunocytochemistry, Western blotting and Flow Cytometry. Fibronectin adhesive human nasoseptal CSPCs are a self-renewing subpopulation, positive for recognized stem cell markers CD24, CD44, CD73, CD90 and CD105 as well as integrins CD29 (beta1) and CD49e (alpha 5). Unlike previous reports for articular CSPCs, they are negative for STRO-1. Nasoseptal CSPCs are clonogenic with increased expression of neuroectodermal cell adhesion molecules and multilineage potential. Nasoseptal CSPCs are distinct from nasoseptal chondrocytes demonstrated by reduced expression of collagen type 1, collagen type 2 and aggrecan in monolayer culture. In addition, CSPCs can regain chondrogenic potential in 3D culture. This cell population may benefit future cell-based cartilage tissue engineering strategies due to its ability to maintain chondrogenicity and chromosomal stability following cell expansion.
Hina W Chaudhry
Icahn School of Medicine at Mount Sinai, USA
Title: Placental Cdx2 cells and cardiac regeneration
Biography:
Abstract:
Introduction: Placenta is an easily available and rich source of multipotent cells. We previously reported that fetal-placental cells “home” to injured maternal hearts with 40% of these cells expressing Cdx2.
Hypothesis: Placental Cdx2 cells could be a novel source for cardiac repair.
Methods: Fetal-derived Cdx2 cells were labeled with EGFP using a cre-lox strategy wherein female virgin B6; 129S6-gt (ROSA) 26Sor<tm1 (CAG-tdTomato*,-EGFP*) Ees>/J43 mice were crossed with male B6. Cg-Tg (Cdx2-cre) 101Erf/J mice. Myocardial infarction (MI) was induced in pregnant mice at mid-gestation. Maternal hearts were analyzed 5 weeks post-MI for Cdx2-derived cardiomyocytes. Cdx2 cells from end-gestation placenta were assayed for cardiac differentiation in vitro. Proteomic analysis, vascular differentiation and immune profiling were carried out and live cell imaging was done to capture spontaneous beating. Additionally, male WT mice was subjected to MI followed by MRI to confirm MI. 1 week post-MI, the test mice received 1 million Cdx2 cells and control mice received equal volume of PBS via tail vein. MRI was repeated 1 and 3 months later to assess the cardiac function.
Results: Cdx2 cells migrated to injured maternal hearts and differentiated into cardiomyocytes. Additionally, Cdx2 cells from the late placenta differentiated into spontaneously beating cardiomyocytes in vitro and expressed cTnt, α actinin and Cx43. The cells also differentiated into vascular cells indicative of multipotentiality. Proteomic analysis identified homing/survival signaling in Cdx2 cells compared to ES cells. Cdx2 cells further displayed a low expression of immune molecules, suggesting they can evade host immune surveillance. MRI analyses after 1 and 3 months showed a significant increase in ejection fraction (EF) in the cell-treated group [deltas: ctrl 0.355±3.421 vs test 17.18±1.05 (**p=.0093) in 1mo and ctrl 3.247±5.09 vs test 19.31±2.59 (*p=.045) in 3 mo]
Conclusion: We demonstrate for the first time that Cdx2 cells from placenta undergo trafficking upon cardiac injury to form cardiomyocytes. Our data imply that placental Cdx2 cells may represent a powerful new therapeutic strategy for cardiac repair.
Cevat Erisken
Nazarbayev University, Kazakhstan
Title: Human bone marrow stem cell behavior on biomimetic nanofiber composites for tendonbone interface regeneration
Time : 14:00-14:25
Biography:
Cevat Erisken has completed his PhD at Stevens Institute of Technology, Hoboken, NJ and served for Columbia University in the City of New York as a Research Assitant Professor. Currently, he is a faculty member in the Department of Chemical Engineering at Nazarbayev University, KZ, and doing research on Biomaterials and Regenerative Medicine. He has published more than 20 articles, lectured at universities and presented at international conferences.
Abstract:
Due to the limited capacity of current reconstruction procedures, there exists a need for new augmentation matrices to improve the biological fixation to obtain a scarless healing at the tendon-bone (TB) interface. The objectives of this study are to 1) fabricate electrospun polycaprolactone (PCL)-based scaffolds containing transforming growth factor (TGF)β3, connective tissue growth factor (CTGF) and nano-hydroxyapatite (nHA), where concentrations of CTGF and nHA change in opposite directions, while TGF-β3 is located in the middle portion of the nanofibrous composites [such organization is expected to contribute to generation of tendon (in CTGF rich zone), fibrocartilage (by TGFβ3) and bone (in nHA rich zone) upon positioning the scaffold in proper zones], 2) establish controlled release of TGFβ3 and CTGF from nanofiber scaffolds, and 3) to investigate human Bone Marrow Stem Cell (h-BMSC) behavior on these scaffolds. Such a design is proposed for the first time, and represents a significant departure from the conventional stratified approach, and is expected to contribute to scar-free TB interface regeneration. Findings show that linearly varying nHA distribution can be accomplished across the scaffold thickness that is also the case in native TB interface. Results also demonstrated that TGFβ3 and CTGF can be incorporated into nanofiber scaffolds with electrospinning, retain its bioactivity, and released in a sustained manner. The h-BMSCs proliferated similarly on graded and individual scaffolds at the end of 14 days. Collagen production by hBMSCs on different scaffold groups did not lead to any significant differences. This study not only reveals the importance of design and use of biomimetic scaffolds in tissue engineering but also yields new insights into the effect of bioactive molecules on interface regeneration by controlling their local availability.
Thazhumpal C Mathew
Kuwait University, Kuwait
Title: Axonal injury induced neurogenesis in the floor of the third ventricle in rat
Time : 14:25-14:50
Biography:
Thazhumpal C Mathew has completed his PhD from the University of Alberta, Canada in 1992 and obtained FRCPath (UK) in 2003. In 1983, he had undergone aresearch training at the University of Lund, Sweden. After his Post-doctoral studies at the University of Alberta, he has worked as Assistant Scientist at NYU, USA. In 1993, he has joined the FAHS of Kuwait University. Currently, he is the Professor and Vice Dean for Research. He was also the Director of the Electron Microscope Unit. His research is in Molecular Neurobiology. He has received several awards and published more than 75 papers and attended over 100 conferences.
Abstract:
Neurogenesis from endogenous neural stem cells might contribute to functional recovery after brain injury. In this regard, the current study is focused on understanding the axonal injury induced neurogenesis at the supraependymal region of the third ventricle in rat using light and electron microscopy. The floor of the infundibulum is lined by a non-ciliated ependyma. Presence of supraependymal cells (SEC) and supraependymal nerve fibers (SEN) that are immersed in the cerebrospinal fluid is a prominent feature of the ventricular floor. In this study retrograde neuronal tracers, fast blue and fluorogold were used to understand the origin of SEN. For monitoring contralateral collateral sprouting and the changes in the SEC following unilateral cervical sympathectomy, sixteen Wistar rats weighing 150-200g were divided into four groups. Group I was used as normal control, group II and III for unilateral and bilateral cervical sympathectomy respectively and group IV as sham control. Fourteen days after the experiment, the ventricular floor was studied. For microscopic analysis, the animals were perfused under anesthesia transcardially with 3% glutaraldehyde and the brains were dissected out and processed. The SEN consist of a mixture of cholinergic, serotonergic and peptidergic nerve fibers. Retrograde tracer analysis showed that at least some of the SEN could originate from the superior cervical ganglia. Fourteen days after unilateral cervical sympathectomy, there was a profound increase in the number of SEN and supraependymal neurons of the infundibular floor. From these studies, it can be concluded that SEC of the third ventricular floor represent another neural stem cell niche that are induced to proliferate and differentiate following axotomy of the SEN.
Biography:
Abstract:
Background & Objectives: Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibition was proved in streptozotocin (STZ)-diabetic rats. The present study aimed at investigating and comparing the therapeutic effect of combined bone marrow mesenchymal stem cells (BMMSCs) with ascorbic acid (AA) and SERCA1a gene transfected MSCs in STZ induced skeletal myopathy of male albino rat.
Methods: Rats were divided into group I of 4 control rats, group II (Diabetic) of 7 rats given intraperitoneal (IP) injection of STZ 50 mg/kg, group III (BMMSCs) of 7 rats given STZ and BMMSCs intravenous (IV), group IV (BMMSCs and AA) of 7 rats given STZ, BMMSCs and AA 500 mg/Kg and group V (SERCA 1a transfected BMMSCs) of 7 rats given STZ andSERCA1a transfected BMMSCs. The rats were sacrificed after 8 weeks.Gastrocnemius specimens were subjected to histological,morphometric, biochemical and statistical studies.
Results: Diabetic rats revealed atypical widely separated and disorganized muscle fibers, loss of striations, some dark nuclei,markedly congested vessels and dense cellular infiltration. Disrupted atypical fibers with no obvious striations and multiple macrophages were evident. A significant increase in the area of atypical fibers, the mean blood glucose level and a significantdecrease in the mean area of pale nuclei, mean area % of CD105 and CD34 +ve cells and of mean PCR values were recorded.The morphological, morphometric and biochemical changes regressed by therapy.Conclusions: The therapeutic effect was found to be more remarkable by combined MSCs and AA administration and mostremarkable by SERCA1a modified MSCs injection.
Biography:
Abstract:
Background & Objectives: Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibition was proved in streptozotocin
(STZ)-diabetic rats. The present study aimed at investigating and comparing the therapeutic effect of combined bone marrow
mesenchymal stem cells (BMMSCs) with ascorbic acid (AA) and SERCA1a gene transfected MSCs in STZ induced skeletal
myopathy of male albino rat.
Methods: Rats were divided into group I of 4 control rats, group II (Diabetic) of 7 rats given intraperitoneal (IP) injection
of STZ 50 mg/kg, group III (BMMSCs) of 7 rats given STZ and BMMSCs intravenous (IV), group IV (BMMSCs and AA)
of 7 rats given STZ, BMMSCs and AA 500 mg/Kg and group V (SERCA 1a transfected BMMSCs) of 7 rats given STZ and
SERCA1a transfected BMMSCs. The rats were sacrificed after 8 weeks. Gastrocnemius specimens were subjected to histological,
morphometric, biochemical and statistical studies.
Results: Diabetic rats revealed atypical widely separated and disorganized muscle fibers, loss of striations, some dark nuclei,
markedly congested vessels and dense cellular infiltration. Disrupted atypical fibers with no obvious striations and multiple
macrophages were evident. A significant increase in the area of atypical fibers, the mean blood glucose level and a significant
decrease in the mean area of pale nuclei, mean area % of CD105 and CD34 +ve cells and of mean PCR values were recorded.
The morphological, morphometric and biochemical changes regressed by therapy.
Conclusions: The therapeutic effect was found to be more remarkable by combined MSCs and AA administration and most
remarkable by SERCA1a modified MSCs injection.
Beatriz Pelacho
Center for Applied Medicine Research, Spain
Title: Therapeutical benefit of epicardial-delivery collagen patches with adipose derived stem cells in rat and pig models of chronic myocardial infarction
Time : 15:15-15:40
Biography:
Abstract:
In recent years, regenerative cell therapy has been widely explored for the treatment of myocardial infarction (MI). However, although transplantation of the stem cell population ADSC (adipose-derived stem cells) in chronic MI is associated with functional improvement, its therapeutic value is limited due to poor long-term cell engraftment and survival. Thus, the objective of our study was to examine whether transplantation of collagen patches seeded with ADSC could enhance cell engraftment and improve cardiac function in models of chronic MI. Chronically infarcted Sprague-Dawley rats (n=58) were divided into four groups and transplanted with media, collagen scaffold (CS), rat ADSC, or CS seeded with rat ADSC (CS-rADSC). Cell engraftment, histological changes, and cardiac function were assessed four months after transplantation. Functional and histological assessments were performed three months post-transplantation. Transplantation of CS-rADSC was associated with increased cell engraftment, significant improvement in cardiac function, myocardial remodeling, and revascularization. Next, their therapeutic potential was tested in a preclinical model of CMI. Gottingen minipigs (n=18) were subjected to MI and then transplanted two months later with CS or CS seeded with pig ADSC (CS-pADSC). transplantation of CS-pADSC in the preclinical swine model improved cardiac function and was associated with decreased fibrosis and increased vasculogenesis. In conclusion, transplantation of CS-ADSC resulted in enhanced cell engraftment and was associated with a significant improvement in cardiac function and myocardial remodeling.