Day 1 :
- Tissue Regeneration | Stem Cell and Regenerative Medicine | Bio Materials | Scaffolds | Tissue Engineering | Regenerative Medicine
Session Introduction
Ken Yaegaki
Nippon Dental University, Japan
Title: Hepatocytes produced from human tooth pulp into swine with cirrhosis: Two transplantation with time interval

Biography:
Yaegaki had received Doctor of Dental Science, and then completed his PhD in Medicine from Kureme University Medical Biochemistry and postdoctoral studies from University of British Columbia. He was trained as an Oral maxillofacial Surgeon at School of Medicine Kurume University. His specialty was facial injuries. He is the director and head of Oral Health at Nippon Dental University, which is the oldest dental school in Asia, also a Dean of PhD program. He has published more than 100 papers and 20 books.
Abstract:
We treated the liver cirrhosis by two step transplantations of hepatocyte produced from human exfoliated deciduous tooth (SHED) into the swine with cirrhosis. SHED at 3 passages was separated by magnetic sorting with CD117 antibody. For hepatic differentiation, CD117+ SHED were grown in DMEM supplemented with insulin-transferrin-selenium-x (ITS-x), embryo-tropic-factors(ETF) and hepatocyte-growth-factor (HGF) for 5days: IMDM supplemented with ITS-x, ETF, HGF, dexamethasone and oncostatin for another 11 days. F344-Nude rats were employed for this study. Carbon tetrachloride (CCl4) was administrated by intraperitoneal injection for 15 weeks to induce cirrhosis. Hepatocyte-like-cells (2 x 106 cells/ animal) suspended in Hank`s Balanced Salt Solution were transplanted into the spleen. The vehicle was injected to the positive control group. Non-cirrhosis-models were used as negative control group. Animals were sacrificed 4 weeks after the transplantation. Then 5 weeks later the sound transplantation was carried out, then the swine were euthanased. Immunocytochemistry observation of the hepatically differentiated cells strongly demonstrated positive staining for albumin, IGF-1, α-feto-protein, HNF4α and CPS-1. The histopathological analysis, HE and Masson’s trichrome staining, indicated a significant decrease of fibrous tissue in the transplantation group with comparing to the positive control group. Healthy liver tissues were recovered by the transplantation. Moreover, serological test results revealed significance differences between the groups. Serum ALT levels of the test group dramatically decreased to one third compared to the positive control group. Activities of albumin, bilirubin, BUN, HA levels were also recovered. By only once transplantation albumin value was improved. but two steps showed much better improvement. The two steps transplantations of hepatocyte-like cells from human tooth transplanted into the liver with severe failure demonstrated their capacity to preform positively because of drastic decreasing fibrous tissues. Together, these findings suggested that two step transplantation is a future potential protocol for treating chronic liver injuries such as cirrhosis.

Biography:
Peter A. Everts is the Chief Scientific Officer at EmCyte Corporation with a demonstrated history of working in the medical practice industry. He is Skilled in Medical Devices for biological therapies for use in Orthobiology-MSK, Spine, Chronic Wound Care, Cardiac Surgery, Reconstructive Surgery, Facial Aesthetics, Hair Regrowth, and other Regenerative Medicine applications. Peter A. Everts is an Strong research professional graduated from the University of Utrecht PhD program, and International ATMO, San Antonio, TX, USA.
Abstract:
Tissue engineering and regenerative medicine offer solutions to a number of compelling clinical problems that have not been adequately addressed through the use of permanent replacement devices. The challenge will be to select the optimal biomaterials, or biological cells, and soluble regulators. Although stem cells hold considerable promise for the treatment of numerous diseases, including cardiovascular disease, musculoskeletal disease, etc. Impediments such as cell harvesting and processing techniques, the control of stem cell fate, cell viability must be overcome before their therapeutic potential can be realized. This requires first of all a meticulous aspiration technique and preparation protocol. Cardiovascular diseases (CVD) are the leading cause of death worldwide, according to a recent report of the American Heart Association. European show that CVD accounts for 45% of all deaths (49% for women and 40% for men) and lead to more than 4 million people deaths every year (1.4 million before the age of 75 years). Acute myocardial infarction (AMI) and chronic ischemic heart disease (IHD) cause significant mortality, morbidity, and treatments result in a growing economic burden. A significant number of these patients develop heart failure due to advanced myocardial remodeling and left ventricular (LV) dysfunction. The existing pharmacological modalities have been able to slow the progression of CVD but have no capacity for reversing or regenerating this process. There is an unmet need for new therapies, including autologous biologics like bone marrow concentrate (BMC), for myocardial repair. Although results from individual trials have been conflicting, emerging evidence from several large meta-analyses of pooled data suggest that therapy with BMC may employ beneficial effects in patients with AMI as well as chronic IHD, enhancing LV function and tissue remodeling, ultimately improving outcomes. Albeit that several trials have been unable to document benefits of BMC therapy, and the overall effects of cell therapy have remained controversial. An explanation for the inconsistency in results might be attributed to differences in trial design, and methods to produce a viable BMC product, containing a significant concentration of mesenchymal cells, with less erythrocyte contamination, a low incidence of hemolysis, and sufficient niche contributors like platelets. This presentation provides a critical overview of the translation of first and second-generation cell types, with particular focus on a new generation of autologous BMC, Aspire-Pure BMC, in relation to the biological differences of previously used BMC products for cardiac repair, to improve cell-based therapies for CVD.
Xiao-Dong Chen
University of Texas Health Science Center, USA
Title: Use of mesenchymal stem cells in anti-aging strategies

Biography:
Chen is a Professor in the Department of Comprehensive Dentistry and Chief of the Regenerative Medicine Program in the School of Dentistry at the University of Texas Health Science Center at San Antonio. His group was the first to establish cell-free native ECM made by bone marrow stromal cells. This system have been using for growing large numbers of high-quality non-hematopoietic stem cells from various sources. To closely replicate the tissue specific microenvironment (niche) ex vivo, Dr. Chen and his team have extended their technology by developing a variety of 3D tissue-specific scaffolds for facilitating stem cell-based applications.
Abstract:
Autologous mesenchymal stem cell (MSC)-based therapies are preferable due to biosafety concerns. In addition, increasing evidence suggests that MSCs may not be immune privileged. However, the quantity and quality of MSCs decline with age and limit the effectiveness and regenerative potential of autologous MSC therapies in elderly patients. Interestingly, we have observed that a sub-population of MSCs (5-10% of the total population) from elderly donors possess a more “youthful” phenotype. The activity of these “youthful” cells in vivo may be deeply suppressed by the aging environment, and the viability of these cells is diminished by harmful factors released by neighboring senescent cells during expansion in culture. In this presentation, I will discuss principles for the use of MSCs in anti-aging, and specifically describe a novel strategy for isolating and expanding this “youthful” subpopulation from elderly patients to bank large quantities of high quality autologous MSCs for treating age-related diseases.
Kara E McCloskey
University of California, USA
Title: Stem cell sources for building vasculature in microfluidic systems

Biography:
Kara E. McCloskey, PhD, is an Associate and Founding Professor in the School of Engineering at the University of California, Merced. She received her BS in Chemical Engineering from The Ohio State University and her PhD through a joint Biomedical Engineering Program with The Cleveland Clinic Foundation. She then completed her postdoctoral training with Dr. Robert Nerem at the Georgia Institute of Technology. Dr. McCloskey’s research is in the field of cardiovascular tissue engineering with a specific focus on deriving functional cell products from stem cells.
Abstract:
Embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells and are attractive in vitro models of vascular development, therapeutic angiogenesis, and tissue engineering. Although a number of biochemical signals have been identified for directing endothelial fate, many of these factors activate redundant pathways, and the minimal combinatorial signals directing vascular fate have yet to be elucidated. Using our stage-specific chemically-defined derivation methodology, we examined multiple combinatorial factors for directing vascular smooth muscle cells (SMCs), perictes, sprouting endothelial cells (ECs) and nonsporting ECs. While all ECs express vascular endothelial (VE-cadherin), the sprouting ECs express low levels of Flt-1 while nonsporting ECs expressing high levels of Flt-1. These cell populations were then examined for their unique potential to generate perfusable vasculature in vitro compared with human umbilical vein endothelial cells (HUVECs) and normal human lung fibroblasts. Results indicate the stem cell-derived populations are more dynamic compare with HUVECs - forming vasculature very early in just 1-2 days, but lack longer-term stability. Further exploration is required for enhancing longer-term stability of vascular networks in vitro.
Joseph Purita
Institute of Regenerative and Molecular Orthopedics, USA
Title: Cutting edge concepts in the use of stem cell and prp injections in an office setting

Biography:
Purita is director of Institute of Regenerative and Molecular Orthopedics (www.stemcellorthopedic.com) in Boca Raton, Florida. Dr. Purita is a pioneer in the use of Stem Cells and Platelet Rich Plasma. He received a B.S. and MD degree from Georgetown Univ. Dr. Purita is board certified in Orthopedics by ABOS. He is a Fellow American College of Surgeons, Fellow American Academy Orthopedic Surgeons, and a Fellow American Academy of Pain Management. He has lectured and taught extensively throughout the world on the use of Stem Cells and Platelet Rich Plasma. He has helped countries develop Stem Cell policies.
Abstract:
The presentation concerns PRP and Stem Cell (both bone marrow, adipose and V-cell) injections for musculoskeletal conditions in an office setting. Indications are given as to which type of cell and technique to use to accomplish repair. Stem cells, both bone marrow derived (BMAC) and adipose, are used for the more difficult problems. PRP injections are utilized for the less severe problems. One aspect of the discussion centers on the newest thinking of PRP in that all components of the blood have importance. Indications are given when to use Stem Cells verses PRP and when to use both. The newest concepts in stem cell science are presented. These concepts include the clinical use of MUSE cells, exosomes, and Very Small Embryonic like stem cells. Basic science of both PRP and stem cells are discussed. This presentation defines what constitutes an effective PRP preparation. Myths concerning stem cells are dispelled. One myth is that mesenchymal stem cells are the most important stem cell. The discussion centers on the fact of the relationship between stem cells and the immune system. Current thinking is that MSCs have an immunomodulation capacity affecting joint chemistry and biology. We now learn in the talk that the hematopoietic stem cells are the drivers of tissue regeneration. Also discussed are adjuncts used which enhance the results. These therapies include supplements, LED therapy, lasers, electrical stimulation, and cytokine therapy. The scientific rationale is presented for each of these entities as to how they have a direct on stem cells.

Biography:
Professor Oleksandr Kukharchuk, MD, Research Director of ReeLabs Pvt. Ltd. He has guided basic research and clinical study in Health Ministry of Ukraine: “In experiments and clinical study, to determine effectiveness of transplantation of stem cells, tissues of fetal and extra-fetal material and tissue therapy by Filatov in immune and onco-pathological process, pancreo- and colonogenic peritonitis, ageing and dysfunction of reproductive system”. He is author of the book “Stem cells: Experiment, Theory, and Clinic. Embryonic, mesenchymal, neural, hematopoietic stem cells”. He was Director of the Coordination Centre for Transplantation of Organs, Tissues and Cells of the Ukraine Health Ministry.
Abstract:
The interactions between stem cells (SCs) and their surrounding microenvironment are pivotal to determine tissue homeostasis and SCs renewal or differentiation in vivo. One of the way for modulation of organ-specific niches for SCs transplantation could be established by using fetal tissue extracts of organs obtained from the stage of incomplete organogenesis, then microenvironment in each of the organs must be specific and enough to generate constant signal for the final SCs differentiation. The objective was to recreate the natural niche microenvironment during cell therapy. We investigated the concentrations of growth factors in tissue extracts of various fetal organs, and studied the efficacy of fetal tissue extracts (FTEs) in patients with non-healing wounds/ulcer who did not respond to previous stem cells treatment. The level of growth factors in the skin, lung, liver, heart, brain, lung and kidney differs considerably. This may be due to differences in regulatory niches that are specific to each organ, which determines the direction of differentiation of the fetal SCs. Treatment included intravenous SCs administration; local multiple injections of SCs along obliterated arteries, around the ulcer, and in the bottom of the wound; and application of FTEs (liver, skin, and muscle) in auto plasma gel. Laser Doppler flow-metry showed the significant improvement of the micro-hemodynamic just 1 month after last administration of FTEs. Selective X-ray contrast arteriography showed the increase of area and expansion of the collateral arterial vasculature. Angiogenesis activation was proved by electronic microscopy, histologically and by immunohistochemistry. Wounds/ulcers have good epithelization and complete healing.
Guriy I. Popov
Pavlov First Saint Petersburg State Medical University, Russia
Title: Influence of mesenchymal stem cells seeding on morphology of tissue-engineered vascular graft based on poly (L-lactide) scaffold

Biography:
Guriy I. Popov graduated from Pavlov Saint-Petersburg State Medical University, Russia (MD, 2012). After that he continues his education as vascular fellow at the same University (vascular surgeon, 2015). Primary spheres of his interest are vascular surgery, cerebrovascular diseases, and tissue engineering. That's why currently he is undergoing research fellowship, with the aim to create TEVG on the basis of PLLA scaffold. He is the vascular surgeon of vascular surgery department PFSMU clinic and the national representative of Russia at ESVT/ ESVS (European society for vascular surgery).
Abstract:
Objective: The evaluation of the effects of adipose-derived mesenchymal stem cells (AD-MSC) on the formation of tissue-engineered vascular graft (TEVG) Materials and methods. Tubular scaffolds 1.1 mm inner diameter were obtained by the electro spinning method on the basis of Nano- and microfibers of poly (L-lactide) (PLLA). AD-MSC was seeded on the scaffolds by the developed filtration method. The subsequent culturing for 14 days was carried out in the constructed flow bioreactor. Cell distribution in the scaffold wall was assessed by the fluorescence microscopy. Obtained grafts were implanted into rat aorta: group 1 without AD-MSC (n=36) with follow-up till 16 months, group 2 with seeded AD-MSC (n=28) with follow-up till 12 months. The material was subjected to histological examination, electron microscopy, immunohistochemistry CD 31+, aSMA and morphometric analysis (cell counting, neointima and neoadventia thickness). To track AD-MSC in vivo PKH-26 labeling and subsequent fluorescence microscopy were performed in 2, 7 and 14 days.
Results: Filtration seeding and subsequent cultivation in the flow bioreactor led to a uniform distribution of AD-MSC in the scaffold wall. Graft patency in the first group was 86%, in the second 96%. All grafts formed neointima, with no signs of hyperplasia in the area of anastomoses. The total resorption of PLLA fibers in group 1 was observed by histological examination, new vascular wall consisted of endothelial lining and connective tissue without smooth muscle cells (SMC); in all cases aneurysm formation was detected. Total cells number of implant wall was more in group 2, including SMC that formed neomedia. Also the outer connective tissue layer was much thicker. Histology identified the uniform formation of new tissues in group 2 with no signs of aneurysm.
Conclusion: AD-MSC seeding leads to the formation of TEVG, morphologically similar to the natural structure of the vessels. The study was supported by Russian Science Foundation (project 14-33-00003)
Ane Garate
Advanced Biological Therapy Unit- UTBA, Spain
Title: Autologous bioscaffolds based on different concentrations of platelet rich plasma and synovial fluid as a vehicle for mesenchymal stem cells

Biography:
Ane Garate completed her PhD in Pharmacy at the University of The Basque Country. During her training she realized a research stay in the department of Biomedical engineering of Case Western Reserve University (Cleveland, U.S.A). Since 2015 she is a member of Advanced Biological Therapy Unit (UTBA) of Mikel Sánchez where she focuses her work in regenerative medicine and cell therapy aplicated in orthopedics.
Abstract:
In the field of tissue engineering, diverse types of bio scaffolds are being developed currently for osteochondral defect applications. In this work, a novel scaffold based on platelet rich plasma (PRP) and hyaluronic acid with mesenchymal stem cells (MSCs) has been evaluated to observe its effect on immobilized cells. The bio scaffolds were prepared by mixing different volumes of synovial fluid (SF) with PRP from patients obtaining three formulations at PRP-SF ratios of 3:1, 1:1 and 1:3 (v/v). The live/dead staining revealed that although the cell number of each type of bio scaffold was different, these constructs provide cells with a suitable environment for their viability and proliferation. Moreover, immobilized MSCs showed their ability to secrete fibrinolytic enzymes, which vary depending on the fibrin amount of the scaffold. Immunohistochemical analysis revealed the positive staining for collagen type II in all cases, proving the biologic action of SF derived MSCs together with the suitable characteristics of the bioscaffold for chondrogenic differentiation. Considering all these aspects, this study demonstrates that these cells-based constructs represent an attractive method for cell immobilization, achieving completely autologous and biocompatible scaffolds.
Roberto Ebensperger
Pontifical Catholic University of Chile, USA
Title: Nano encapsulation of Stem Cells and Cell Targeting

Biography:
Roberto Ebensperger is Associate Professor of Clinical Pharmacology and Director of the Laboratory of Cellular Therapy and Regenerative Medicine in the Pontificia Universidad Catolica de Chile. He is Pharmacist and PhD in Biochemistry from the Universidad de Chile. He has had several postdoctoral training in molecular cardiology at Medizinische Hochschule Hannover, hair follicle biology and pathology at Centre for Skin Sciences, University of Bradford, hematology and aging biology at Université Pierre et Marie Curie Paris VI. He was invited professor at Equipe Biologie Cellulaire du Vieillissement, Université Pierre et Marie Curie. Currently, he is interested in mesenchymal stem cell applications in wound healing. In 2013 he founded Plasticel, a spin-off company that initiated R&D activities in applications for cellular therapy for plastic surgery and baldness.
Abstract:
Cell nanoencapsulation is a novel delivery system based on a self-assembly technique mediated by electrostatic interactions called Layer-by-Layer (LbL) deposition, that do not significantly increase cell/implant volume because of the nanometric thickness of its layers. LbL depositions could coat the entire surface of individual cells, providing mechanical resistance to cells against manipulation and storage conditions prior to implantation in the patient. LbL nano capsulation are formed over the cell by the sequential deposition of layers of polymers, which are mediated by opposite electrostatic interactions when alternating polymers of opposite charge over an, also charged, template. Using this technology, nano capsulation of single-cells of human adipose-derived mesenchymal stem cells (ADSC) was possible and experimental factors to successfully preserve viability and functionality of cells, in order to be used in regenerative medicine applications, were assessed. Additionally, our nanoencapsulation method of mesenchymal stem cells (MSC) is useful for cell targeting by conjugating a specific antibody. Increased cell attachment over HUVEC cells was observed by using a specific anti-CD31 conjugated on ADSC. Conjugation of a specific antibody to the nanolayer increases specific cell recognition and, possibly, tissue engraftment. Thus MSC, through cell nanoencapsulation, may serve as a promising platform for cell-based tissue engineering and targeted cell delivery, in the regenerative medicine and cell therapy. Layer-by-Layer Nano encapsulation and potential practical applications. As indicated in the figure, nanoencapsulation of MSC could be useful for example for: A) cell targeting by conjugating a specific antibody; B) tissue engineering by incorporating a matrix protein that could be used as scaffold; and C) immunoisolation when using multilayer nanoencapsulation.
Dimosthenis Mavrilas
University of Patras, Greece
Title: Production of electrospun biodegradable PVA nanofiber membranes for tissue engineering scaffold design

Biography:
Dimosthenis Mavrilas is an Associate Professor of Biomedical Engineering in the University of Patras, Greece. He has completed his PhD in Biomechanics from the University of Patras. He has published more than 30 papers in the fields of Biomechanics and Biomaterials, as well in Scaffolds for Tissue Engineering.
Abstract:
Electro spinning is an attractive technique by which we can produce fibrous biodegradable polymeric scaffolds for tissue engineering (TE) applications. Polyvinyl Alcohol (PVA) is a biodegradable, biocompatible polymer with a fast hydrolytic degradation rate due to its hydrophylicity, which however makes it suitable for cell viability and function. The combination of hydrophilic (cytocompatible) with hydrophobic (less cytocompatible but mechanically strengthen and more resistant to degradation) polymers may result in a suitable polymer scaffold design. In the present work, we aimed to produce PVA polymeric membranes, as a potential part of a composite polymeric TE scaffold, with specific nanofiber architecture, giving special attention to the orientation of the fibers and, hence, controlling the final mechanical behavior to match that of the physiological tissues to be replaced. To this end, we used a specifically designed and constructed drum collector for our custom made electro spinning system, with accurate angular velocity control, and tested different electro spinning parameters (concentration of polymer aquatic solution, transfer rate, needle-collector distance, applied high voltage and angular frequency) to obtain optimization of the design. SEM results showed that the fiber diameters ranged from 200 400 nm, with a good quality of fiber appearance. Fiber orientation was directly related to the angular velocity (or rotational speed) of the drum collector (500, 1000, 1500 and 2000 rpm). Tensile testing up to breaking point, to assess Young’s modulus and Ultimate tensile strength and strain, as well contact age measurements to assess scaffold’s hydrophylicity are currently running.
Woodring E. Wright
UT Southwestern Medical Center, USA
Title: The creation of artificial lungs from decellularized tissue

Biography:
Woodring E. Wright Professor of Cell Biology and Southland Financial Corporation Distinguished Chair in Geriatric Research. He received his BA degree, Summa Cum Laude, from Harvard University in 1970, a PhD under the direction of Dr. Leonard Hayflick in 1974 and an MD from Stanford University School of Medicine in 1975. Following a postdoctoral fellowship at the Pasteur Institute in Paris, France with Dr. Francois Gros, he joined the faculty at Southwestern Medical School in Dallas, Texas in 1978.
Abstract:
Lung failure is a major health problem, both in genetic disorders such as cystic fibrosis and following environmental insults in diseases such as emphysema and idiopathic pulmonary fibrosis. The restricted availability of histocompatible human lungs for transplantation is often a rate limiting factor for treatment. Transplanting both lungs increases patient long-term survival, but the shortage of lungs makes this controversial since it halves the number of recipients. This problem would be solved by being able to create two lungs for each patient. Lung transplantation is further complicated by chronic transplant rejection; after receiving a transplant a patient must be on immune-suppressing drugs for the rest of their lives even after tissue matching. This long term immunosuppression has significant side effects and allows only <20% of recipients to survive more than 10 years after transplantation. We will avoid both immunological and availability problems by using a patient’s own bronchial epithelial and endothelial cells to create two lungs. Previous approaches to populating decellularized lungs with bronchial epithelial and endothelial cells have met with only limited success. The introduced cells differentiated rapidly, producing only small foci of normal appearing alveolar or conducting airway histology, widely separated from other foci containing capillaries. We are overcoming these limitations by a variety of interventions to temporarily block differentiation and stimulate both proliferation and migration. Some of these approaches use chemical reagents, while others exploit oncogenes. A large number of oncogenes are known to block differentiation, and stimulate both migration and proliferation. In preliminary experiments, we are introducing them and simply analyzing their effects on colonization of the decellularized lungs. In later experiments, these oncogenes will be under the control of inducible promoters or in cre-lox excisable constructs. All constructs will contain herpes-virus TK suicide cassettes, so that any cells that escaped excision by cre could still be eliminated by treatment with ganciclovir if they began to proliferate excessively. Ultimately, we hope to be able to create transplantable lungs on demand for specific patient’s from their own stem cells, thus avoiding any need for ongoing immunosuppression.
Elizabeth G. Loboa
University of Missouri, USA
Title: Tissue engineering and regenerative medicine in the age of multi-drug resistant bacteria

Biography:
Elizabeth Loboa is Dean and Professor of Bioengineering in the College of Engineering at the University of Missouri, Columbia. She received her B.S. in Mechanical Engineering from the University of California, Davis and her M.S. and PhD in Biomechanical Engineering and Mechanical Engineering, respectively, from Stanford University. Although dean, she continues to maintain an active research portfolio with work in her laboratory focused on: 1) biomimetic mechanical, electrical and material stimuli to human stem cells for functional tissue engineering applications; and, 2) textile-based and nanofibrous “smart bandages” as controlled release systems for wound healing, tissue engineering, and regenerative medicine applications requiring antimicrobial, antibacterial, and/or anti-inflammatory treatment(s). Dr. Loboa has published over 275 peer-reviewed conference proceedings, book chapters and journal articles.
Abstract:
In this presentation, Dr. Loboa will discuss approaches in her lab to elucidate and optimize biomimetic smart materials for tissue engineering and regenerative medicine applications using human adipose derived stem cells (hASC). Human ASC are a particularly promising cell source for functional tissue engineering applications due to their multiline age differentiation potential and their abundance and ease of harvest relative to many other cell types. Focus will be placed on regeneration of skin and musculoskeletal tissues; and, approaches to wound care and tissue regeneration while combating multi-drug resistant bacteria, in particular methicillin resistant Staphylococcus Aureus (MRSA).
Glenn R Gaudette
Worcester Polytechnic Institute, USA
Title: Development of a vascularized scaffold from spinach leaves

Biography:
Glenn R. Gaudette, PhD, is a Professor of Biomedical Engineering at Worcester Polytechnic Institute. He received his PhD in Biomedical Engineering from SUNY – Stony Brook. He has over 75 publications, co-edited a book on Cardiovascular Regeneration, has 4 issued patents and founded a company based on the technology developed in his laboratory. His research, which is supported by the National Institutes of Health and the National Science Foundation, aims to develop a treatment for the millions of Americans suffering from myocardial infarction and other cardiovascular diseases. He has pioneered the use of plants as scaffold for heart regeneration. His work has been featured throughout the world including the BBC, The Washington Post and Fox National News. His work was named one of the top medical breakthroughs of the year by Boston Magazine and was the 7th Most Popular Stories of 2017 in National Geographic. Dr. Gaudette also teaches biomedical engineering design and innovation, biomechanics and physiology. He promotes the development of the entrepreneurial mindset in his students through support provided by the Kern Family Foundation. He was named the 2015 Faculty Member of the Year by the Kern Entrepreneurial Engineering Network. Dr. Gaudette also participates in multiple faculty governance committees at WPI and enjoys working with WPI students in the classroom, on projects and on research projects.
Abstract:
One of the major obstacles in growing replacement tissue is the inability to deliver oxygen, nutrients, and essential molecules required for cells to survive. To overcome this limitation, we have developed an unconventional approach that involves crossing the plant and animal biological kingdoms. The veins in spinach leaves are remarkably similar to the veins and arteries in human hearts. By removing the plant cells using a technique developed for mammalian organs and tissues, a cellulose structure with a branching network of vessels that can distribute fluid is left behind. The spinach veins remain patent after this process and allow the passage of microsphere approximately the same size as red blood cells. This scaffold supports human cell attachment, including contracting human heart muscle cells. The crossing of biological kingdoms may allow for new biomaterials with multiple applications in tissue engineering.

Biography:
Joel I. Osorio is the CEO & Founder - Biotechnology and Regenerative Medicine at RegenerAge International ™ (www.regenerage.clinic) VP of International Clinical Development for Bio quark, Inc. (www.bioquark.com) Chief Clinical Officer at ReAnima™ Advanced Biosciences (www.reanima.tech) Westhill University School of Medicine. Mexico Advance Fellow by the American Board of AntiAging and Regenerative Medicine (A4M) Visiting scholar at University of North Carolina at Chapel Hill (Dermatology) Fellow in Stem Cell Medicine by the American Academy of Anti-Aging Medicine and University of South Florida.
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.2-37 One method of reprogramming somatic cells into pluripotent stem cells is to expose them to extracts prepared from Xenopus laevis oocytes1 We showed previously that coelectroporation of Xenopus laevis frog oocytes; with normal cells and cancerous cells lines, induces expression of markers of pluripotency.4 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 squalenemonohydroperoxide (Paylian et al, 2016). 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 (Paylian et al, 2016). Because of ethical reasons, legal restrictions, and a limited numbers 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 SureScan5-6 . Based on the of electrical stimulation for rehabilitation and regeneration after spinal cord injury published by Hamid and MacEwan 8-9 , we designed an improved delivery method for the in situ application of MSCs and Bioquantine® in combination with the RestoreSensor® SureScan® Conclusions: 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 month 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 sensitivity110-11.
Shaik O. Rahaman
University of Maryland, USA
Title: TRPV4 channels regulates matrix stiffness and TGFβ1-induced epithelial-mesenchymal transition

Biography:
Shaik O. Rahaman, PhD, is an Assistant Professor at the University of Maryland, USA. His laboratory is interested in elucidating the signaling events underlying the pathogenesis of atherosclerosis and fibrosis. Dr. Rahaman earned his PhD in Molecular Biology at Jadavpur University, and a BS in Human Physiology (Honors), and an MS in Biophysics and Molecular Biology from University of Calcutta. From 2000-2014, Dr. Rahaman worked at Cleveland Clinic, Cleveland, USA, as a Postdoctoral Fellow, eventually as a Project Scientist and Assistant Professor. He was the recipient of the American Heart Association Scientist Development Grant, NIH-R01 grant, and NSF grant. Dr. Rahaman is the author or co-author of 23 research papers in high impact international peer-reviewed journals of repute. Dr. Rahaman has given numerous invited talks nationally and internationally, and is a reviewer/editorial board member in numerous scientific journals. Dr. Rahaman also served as a reviewer for National Institute of Health (USA).
Abstract:
Epithelial-mesenchymal transition (EMT) has critical functions in cellular processes including development, tissue healing, and oncogenesis. Emerging data support a role for both a mechanical signal, and a biochemical signal, in EMT. We report evidence showing that transient receptor potential vanilloid 4 (TRPV4) channel, is the likely mediator of EMT in response to both transforming growth factor β1 (TGFβ1), and matrix stiffness. We found that: i) genetic deficiency of TRPV4 channel blocked TGFβ1-induced EMT in normal mouse primary epidermal keratinocytes (NMEKs) as determined by changes in morphology and alterations of expression of EMT markers including E-cadherin (ECAD), N-cadherin (NCAD), and α-smooth muscle actin (α-SMA); and ii) TRPV4 deficiency prevented matrix stiffness-induced EMT in NMEKs. Intriguingly, TRPV4 deficiency in mice suppressed expression of mesenchymal markers, NCAD and α-SMA, in murine dermal fibrosis model. We found an increased co-localization of TRPV4 with NCAD, and decreased co-localization of TRPV4 with epithelial marker ECAD in skin tissues of bleomycin-treated wild-type mice compared to saline controls. Mechanistically, our results showed that: i) TRPV4 was critical for the nuclear translocation of YAP/TAZ (Yes-associated protein/transcriptional coactivator with PDZ- binding motif) in response to matrix stiffness and TGFβ1, ii) TRPV4 deletion inhibited both matrix stiffness- and TGFβ1- induced expression of YAP/TAZ proteins, and iii) TRPV4 deletion abrogated both matrix stiffness- and TGFβ1-induced activation of AKT, but not Smad2/3. Altogether, these data identify a novel role for TRPV4 in regulating EMT.
Shagidulin Murat
I.M. Sechenov First Moscow State Medical University, Russia
Title: Usage of tissue engineering for stimulation reparative processes in damaged liver

Biography:
Shagidulin Murat has completed his PhD at the age of 47 years from Federal State Budgetary Institution «Academician V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs». Moscow. Russia. He is Head of experimental transplantology and artificial organs department Federal State Budgetary Institution «Academician V.I.Shumakov Federal Research Center of Transplantology and Artificial Organ», Ministry of Health of the Russian Federation; and Deputy Head Department of transplantology and artificial organs I.M.Setchenov Moscow state Medical University. He has published more than 187 papers in reputed journals.
Abstract:
Background: Tissue engineering and cell therapy is a new perspective method for recovery function and the formation of new centers of regeneration of damaged organs.
Aim: Creating technology for the treatment of chronic liver failure (CLF) by growing the functionally active liver tissue and its regeneration.
Methods: (CLF) was modeled on Wistar rats by means of ССl4. Mesenchymal stromal cells of bone marrow (MSC) were obtained from August rats by standard procedure. MSC (0, 5-0,8х106cells/cm3) was cultivated for 10 days and then applied on the composition of heterogenic implantable hydrogel. Formed cell engineering constructions (CECs) were implanted into damaged rat liver. The animals were divided into 2 groups: control gr.1 (n=25) without treatment-injected saline and with treatment-gr.2 (n=25). Dynamics reduction of CLF; liver and CECs morphology were investigated within 365 days after implantation.
Results: In gr.1 took place mortality (48%), the formation of liver cirrhosis without recovery. In gr.2 all biochemical indices returned to normal levels within 30-60. On 90 days it was shown restoration of a hepatic lobe structure and liver architectonics, viable and proliferative activity of MSC. Also detected neogenic plethoric vessels and neogenic bile ducts were detected.
Conclusion: Studies found out that the proposed method of implantation CECs with MSC is effective method for stimulation of reparative regeneration in the damaged liver, treatment CLF and can be used in clinical practice.
Takashi Tsuji
RIKEN Center for Bio systems Dynamics Research, Japan
Title: Functional 3d-organ regeneration as a future organ replacement therapy

Biography:
Takashi Tsuji has completed PhD from Niigata University and worked in JT Inc. He was Professor of Tokyo University of Science (2000-14) and is Team leader of RIKEN BDR (2014-Present). He is Visiting Professor of Kobe University, Tokyo Dental University, Kwansei University, Tokyo University of Science and Keio University. He has published more than 100 papers including review in journals and has been serving as an editorial board member of Scientific Reports. He is a Director of Organ Technologies Inc.
Abstract:
In this decade, great progress has been made in the field of organ regeneration by incorporating the concept emerged from stem cell biology and developmental biology, pioneering a new frontier in regenerative medicine. Generation of bioengineered organ germ utilizing fate-determined organ-inductive epithelial and mesenchymal cells proofed the concept of functional organ regeneration in vivo. Organoid studies verified that almost all organs can be generated as mini-organ by recapitulating embryonic body patterning and establishment of organ-forming field in self-organized pluripotent stem cells utilizing cytokines mimicking patterning and positional signals during organogenesis. We previously developed an in vitro three dimensional stem cell culture to form a three-dimensional bioengineered organ germ in the early developmental stages, termed the ‘bioengineered organ germ method’ (Nature Methods, 2007). We investigated the potential of the bioengineered organ germs of ectodermal organs including tooth (PNAS, 2009), hair follicle (Nature Common., 2012) and secretory organs (Nature Commun., 2013, Nature Common., 2013) for functional organ replacement in vivo. Recently, we generated a bioengineered three dimensional integumentary organ systems including skin appendages such as hair follicle and sebaceous gland from induced pluripotent stem (iPS) cells (Science Adv., 2016). In this symposium, I would like to talk and discuss the current trend of researches aiming functional regeneration of three-dimensional (3D) organ. I also discuss the potential usage of recent achievements and introduce a plan of a first-in-human clinical study of autologous hair follicle regeneration as a future direction to realize the next-generation organ replacement regenerative therapy.
Christelle Monville
University of Evry Val d' Essonne, France
Title: Preclinical validation of a tissue engineered product consisting in RPE derived from human embryonic stem cells disposed on human amniotic membrane in rats and non-human primates

Biography:
Christelle Monville has completed his PhD at the age of 28 years from Créteil University and postdoctoral studies from Cardiff University. Christelle Monville is a current professor at Evry’s University (France). The objectives of her group (Istem, www.istem.eu) are (1) to develop pre-clinical studies required for the development of human pluripotent stem cells cellular therapy for the treatment of a number of monogenic retinal diseases and (2) disease modeling and drug discovery using patient-specific human induced Pluripotent Stem (hiPS). Recently, her group has successfully developed, under clinically compatible conditions, a tissue-engineered product (TEP) consisting of RPE cells derived from hESCs disposed on a biocompatible substrate. These results are supportive for the initiation of our phase I/II clinical trial to treat RP patients.
Abstract:
In developed countries, retinal degenerative diseases affecting Retinal Pigmented Epithelium (RPE), including Age-related Macular Dystrophy and inherited retinal diseases such as Retinitis Pigmentosa (RP), are the predominant causes of human blindness worldwide. Despite the scientific advances achieved in the last years, there is no cure for such diseases. In this context, we have developed a cell therapy medicinal product based on our expertise in tissue engineering and in the manipulation of pluripotent stem cells. This novel tissue engineered product (TEP) consists in RPE cells derived from clinical grade human embryonic stem cells disposed on a biocompatible substrate allowing the formation of a 3D functional sheet, suitable for transplantation. After functional validation in a rodent model of RP (Ben M'Barek et al., 2017), our purpose was to test the safety of the surgery and local tolerance in non-human primates (NHP). A specific device was developed in order to (i) embed the TEP in gelatin, (ii) allow its transport in a specific medium and (iii) cut the transplant at the right format. Non-human primates (NHP, n=6) were transplanted in one eye (right eye) with the TEP in the macular region. Left eye was left untreated. Retinal integrity and functionality were assessed at different time points through Eye fundus, Optical-coherence tomography (OCT) and electroretinography (ERG). Inflammation was also assessed using slit lamp. At the end of the experimental period, histological analysis was performed to evaluate the correct location and integration of the TEP within the host retina. We have shown in NHP that our surgical method of implantation was safe and did not provoke any local inflammation or retinal deterioration. Morphologic and histologic studies indicated that RPE cells were integrated into the host retina and were able to interact with photoreceptors. Our results lay the foundations for clinical studies early 2019.

Biography:
Padma priya has research experience, and history of working in the hospital & health care industry. Skilled stem cells therapy protocol from preparation to treatment with 15 scientific publications. Established efficacy of stem cells in clinical research. Strong research professional with a Masters focused in Biotechnology from Saint-Petersburg State Chemical Pharmaceutical Academy (Russia). Field of interest: ageing, prenatal stem cells, exosomes, 3D progenitor cell cultures, stem cell niche modeling.
Abstract:
The aging theory of the body stem spaces depletion was published in 2011 [Medicine Today and Tomorrow, 50-51, (1-2): 292-310], where we showed the decrease of stem cells resources in the aging. In order to restore all functional system of the body we require to increase organ and tissue specific stem cells reserve in the whole body: In brain, heart, lungs, vessels, liver, kidneys, bone marrow, tissue of immune and endocrine systems, organs of vision and hearing, skin, muscles and bone tissue. Goals of stem cells rejuvenation program: eliminate aging changes of vital physiological system and prevent them from aging; eliminate or to stop ageing disease development; normalize ratio of biological and chronological age; restore function of immune system; rejuvenate hair, face, neck, décolleté, and hand skin. We study dynamics of biological and chronological age ratio, Frailty Index, frequency of aging symptoms, viscoelastic parameter skin, roughness, radiance and uniformity of hand skin tone. Evaluation results of hand, neck, décolleté and face skin rejuvenation conducted by Global Aesthetic Improvement Scale (GAIS). Investigations were performed during 60 months. Maximum level of deformation of the skin reduced simultaneously to increase in its elasticity on the span of the whole observation period. Patients GAIS results: optimal cosmetic results – 78.9%; significant improvement but not complete correction – 9.7%; improvement, but required additional correction – 11.3% (all women with deformable type of face of aging). The program significantly reduces the biological age, and Frailty Index that evidences about the decrease in risk of aging disease appearance.
Irina I. Suvorova
Institute of Cytology of the Russian Academy of Sciences, Russia
Title: The regulation of autophagy in embryonic stem cells

Biography:
Irina I. Suvorova is Senior Researcher at Laboratory of molecular mechanisms of cell differentiation of Institute of Cytology of the Russian Academy of Sciences. Suvorova received Bachelor’s and Master’s degrees from Saint-Petersburg State University in Molecular biology Science and her PhD from Institute of Cytology of the RAS under the supervision of Professor Valery A. Pospelov. Her current research focuses on research of fundamental features of embryonic stem cells including the mechanisms of pluripotency maintenance in cells cultured in vivo. Her research is supported by the Russian Foundation for Basic Research (RFBR) and by the Russian Science Foundation (RSF). At present time Irina Suvorova has received a Presidential scholarship as a support for her research in the field of autophagy research in embryonic stem cells.
Abstract:
Embryonic stem cells (ESCs) possess the remarkable ability of continuous replication and have the capacity to generate differentiated cells comprising all three embryonic germ layers. Under favorable culture conditions ESCs could be successfully maintained in a proliferative and pluripotent state that creates the possibility of their therapeutic application in regenerative medicine. However, ESCs become heterogeneous after long-term passaging in vitro as evidenced by morphological changes, reduced self-renewal and spontaneous differentiation. Hence, the maintenance of genetically stable pluripotent stem cells after long-term in vitro culture is one of the most important tasks in the field of cell therapy. Autophagy, a major intracellular degradation pathway essential for cellular and energy homeostasis, functioning in the clearance of misfolded proteins and damaged organelles, is conserved from yeast to mammals. Over the last decade, autophagy has thus become an important biological process to study owing to its implications in various human physiological and pathological conditions, including development, immunity, cancer, neurodegeneration and longevity. It can be assumed that spontaneously arising differentiated ESCs in vitro as well as ESCs carrying mutations in vitro originate from the cells with deregulated autophagy. Therefore, in this project is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in ESCs.
Alain Chapel
Pierre-and-Marie-Curie University, France
Title: Stem cell therapy for the treatment of severe tissue damage after radiation exposure

Biography:
Alain Chapel currently works at the Department of man radio-protection, Institute of Radioprotection and Nuclear Safety (IRSN).For the past 25 years, Alain Chapel has been developing gene and cell therapy using non-human primates, immune-tolerant mice and rats to protect against the side effects of radiation. He collaborates with clinicians to develop strategies for treatment of patients after radiotherapy overexposures. He has participated in the first establishment of proof of concept of the therapeutic efficacy of Mesenchymal stem cells (MSCs) for the treatment of hematopoietic deficit, radio dermatitis and over dosages of radiotherapy. He has contributed to the first reported correction of deficient hematopoiesis in patients (graft failure and aplastic anemia) thanks to intravenous injection of MSCs restoring the bone marrow microenvironment, mandatory to sustain hematopoiesis after total body irradiation. He is scientific investigator of Clinical phase II trial evaluating the efficacy of systemic MSC injections for the treatment of severe and chronic radiotherapy-induced abdomino-pelvic complications refractory to standard therapy (NCT02814864Hirsch Index 26.
Abstract:
The late adverse effects of pelvic radiotherapy concern 5 to 10% of them, which could be life threatening. However, a clear medical consensus concerning the clinical management of such healthy tissue sequelae does not exist. Our group has demonstrated in preclinical animal models that systemic MSC injection is a promise approach for the medical management of gastrointestinal disorder after irradiation. We have shown that MSC migrate to damaged tissues and restore gut functions after irradiation. The clinical status of four first patients suffering from severe pelvic side effects resulting from an over-dosage was improved following MSC injection in a compassional situation. A quantity of 2x106 - 6x106 MSC /kg were infused intravenously to the patients. Pain, hemorrhage, frequency of diarrheas and fistulisation as well as the lymphocyte subsets in peripheral blood were evaluated before MSC therapy and during the follow-up. Two patients revealed a substantiated clinical response for pain and hemorrhage after MSC therapy. In one patient pain reappeared after 6 months and again substantially responded on a second MSC infusion. A beginning fistulisation process could be stopped in one patient resulting in a stable remission for more than 3 years of follow-up. The frequency of painful diarrhea diminished from an average of 6/d to 3/d after the first and 2/d after the 2nd MSC injection in one patient. In all patients, prostate cancer remained in stable complete remission. A modulation of the lymphocyte subsets towards a regulatory pattern and diminution of activated T cells accompanies the clinical response in refractory irradiation-induced colitis. No toxicity occurred. MSC therapy was safe and effective on pain, diarrhea, haemorrhage, inflammation, fibrosis and limited fistulisation. For patients with refractory chronic inflammatory and fistulising bowel diseases, systemic MSC injections represent a safe option for salvage therapy. A clinical phase II trial will start in 2018.
Maha Azzam
Mansoura University, Egypt
Title: Insulin-producing cells from adult human bone marrow mesenchymal stem cells control chemically-induced diabetes in dogs

Biography:
Maha Azzam received her Bachelor in veterinary medicine from University of Mansoura at 2012, completed diploma of clinical biochemistry in 2014 and completed his Master degree of animal physiology at the age of 27 years from Veterinary Medicine Mansoura University, her master title is impact of insulin producing stem cells derived from human bone marrow on some diabetic complications. She is a research veterinarian at biotechnology department in Urology and Nephrology center Mansoura University’s he has published 2 papers in stem cells for diabetes treatment.
Abstract:
Evidence was provided that human bone marrow-derived mesenchymal stem cells (HBM-MSCs) could be differentiated to form insulin- producing cells (IPCs). The efficacy of these cells to control diabetes in large animals was carried out to evaluate the sufficient number of cells needed/kg body weight and to determine the functional longevity in vivo. Ten male mongrel dogs weighting 15-20 kg were used in this study. Diabetes was chemically-induced in 7 dogs by a mixture of alloxan and streptozotocin. Three non-diabetic dogs served as normal controls. Differentiated HBM-MSCs (5 million /Kg) were encapsulated in Theracyte capsules and transplanted beneath the rectus sheath. Each dog received 2 capsules. One dog died 4 days postoperative from inhalation pneumonia. The remaining 6 dogs were followed up for 6-18 months. Four dogs became norm glycemic within 6- 8 weeks with normal glucose tolerance curves providing evidence that the transplanted cells were glucose-sensitive and insulin-responsive. In the remaining 2 dogs, fasting blood glucose was reduced but did not reach euglycemic levels. The sera of all transplanted dogs contained human insulin and c-peptide but negligible levels of canine insulin. When the HBM-MSCs- loaded capsules were removed, rapid return of diabetic state was noted. The harvested capsules were examined by immunofluorescence. IPCs were seen and co-expression of c- peptide was confirmed. Furthermore, all the pancreatic endocrine genes were expressed by the transplanted cells. Conclusions: This study provided evidences that Theracyte capsules could protect the xenogeneic HBM-MSCs from the host immune response. This is an important issue when clinical stem cell therapy is considered for definitive treatment for T1DM.
Wael Abo Elkheir
Military Medical Academy, Egypt
Title: Stem Cell Therapy in Obstetrics and Gynecology

Biography:
Dr. Wael Abou Elkheir, also known as Wael AE, M.D. has been the Vice president of Egyptian Society of Stem Cell Research since August 21, 2008. Dr. Wael serves as a Major General of the Egyptian Armed Forces & a Professor of Microbiology & Immunology at Military Medical Academy. He served as a Member of the National Stem Cell Committee of the Egyptian Ministry of Health. He served as Head of Stem Cell Therapy Unit, Sheikh Zayed Specialist Hospital, and Egyptian Ministry of Health. Dr. Wael is one of the country's leading Stem cell researchers and therapy in many untreatable and devastating disorders.
Abstract:
Reproductive tissues are now recognized as sources of stem/progenitor cells and as targets for regenerative medicine. This presentation briefly reviews the progress and future challenges of applying regenerative medicine to the urogenital tract and the use of stem cells for the treatment of inherited genetic diseases, especially those with irreversible perinatal damage. Stem cells sourced from reproductive tissues have been used or investigated for their potential use in other areas such as hematological disease, traditionally treated with hematopoietic stem cells (HSC) from adult sources but for which toxic adjuvant treatments, or bone tissue engineering, are concurrently needed. However, applications of such methods, together with the use of stem cells for gamete generation, are beyond the scope of this ppt. briefly, stem cells have two properties. The first is the ability to self–renew or undertake numerous cell divisions, while maintaining an undifferentiated state. The second is that of multipotency; the capacity to differentiate into a mature cell type. Totipotent stem cells, from the morula, can differentiate into embryonic and extra embryonic cell types, and can produce a complete and viable organism. Pluripotent stem cells descend from totipotent cells and differentiate into tissues derived from any of the three germ layers, including fetal tissues (amniotic fluid cells, the amnion, umbilical cord and placenta). Multipotent stem cells differentiate into various tissues originating from a single germ layer, for example, mesenchymal or haemopoietic stem cells. Unipotent cells such as muscle satellite cells on the other hand, produce only their own cell type but show greater self–renewal than fully mature cells. Theoretically, the more primitive or “potent” a stem cell is, the more predisposed it is to uncontrolled cell division, and the greater its potential for oncogenesis. Although there is some concern regarding the oncogenic potential of pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells, nonpluripotent cell sources are not inherently oncogenic. Embryonic stem (ES) cells offer the prospect of novel treatments in regenerative medicine although progress here has been impeded by controversies surrounding the source. However, multipotent cells are now being isolated from several tissues, readily obtained as products of diagnostic tests, at disruption of pregnancy and at birth. In the field of gynecology, regenerative medicine approaches to repair or replace damaged or diseased urogenital tract organs, such as the urinary sphincter, pelvic floor, uterus, ovaries and vagina, are currently in the preclinical and clinical phases of study. In obstetrics, the area of stem cell transplantation has been largely focused on adult stem cell therapy
Wael Abo Elkheir
Military Medical Academy, Egypt
Title: Stem Cell Therapy in Obstetrics and Gynecology

Biography:
Dr. Wael Abou Elkheir, also known as Wael AE, M.D. has been the Vice president of Egyptian Society of Stem Cell Research since August 21, 2008. Dr. Wael serves as a Major General of the Egyptian Armed Forces & a Professor of Microbiology & Immunology at Military Medical Academy. He served as a Member of the National Stem Cell Committee of the Egyptian Ministry of Health. He served as Head of Stem Cell Therapy Unit, Sheikh Zayed Specialist Hospital, and Egyptian Ministry of Health. Dr. Wael is one of the country's leading Stem cell researchers and therapy in many untreatable and devastating disorders.
Abstract:
Reproductive tissues are now recognized as sources of stem/progenitor cells and as targets for regenerative medicine. This presentation briefly reviews the progress and future challenges of applying regenerative medicine to the urogenital tract and the use of stem cells for the treatment of inherited genetic diseases, especially those with irreversible perinatal damage. Stem cells sourced from reproductive tissues have been used or investigated for their potential use in other areas such as hematological disease, traditionally treated with hematopoietic stem cells (HSC) from adult sources but for which toxic adjuvant treatments, or bone tissue engineering, are concurrently needed. However, applications of such methods, together with the use of stem cells for gamete generation, are beyond the scope of this ppt. briefly, stem cells have two properties. The first is the ability to self–renew or undertake numerous cell divisions, while maintaining an undifferentiated state. The second is that of multipotency; the capacity to differentiate into a mature cell type. Totipotent stem cells, from the morula, can differentiate into embryonic and extra embryonic cell types, and can produce a complete and viable organism. Pluripotent stem cells descend from totipotent cells and differentiate into tissues derived from any of the three germ layers, including fetal tissues (amniotic fluid cells, the amnion, umbilical cord and placenta). Multipotent stem cells differentiate into various tissues originating from a single germ layer, for example, mesenchymal or haemopoietic stem cells. Unipotent cells such as muscle satellite cells on the other hand, produce only their own cell type but show greater self–renewal than fully mature cells. Theoretically, the more primitive or “potent” a stem cell is, the more predisposed it is to uncontrolled cell division, and the greater its potential for oncogenesis. Although there is some concern regarding the oncogenic potential of pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells, nonpluripotent cell sources are not inherently oncogenic. Embryonic stem (ES) cells offer the prospect of novel treatments in regenerative medicine although progress here has been impeded by controversies surrounding the source. However, multipotent cells are now being isolated from several tissues, readily obtained as products of diagnostic tests, at disruption of pregnancy and at birth. In the field of gynecology, regenerative medicine approaches to repair or replace damaged or diseased urogenital tract organs, such as the urinary sphincter, pelvic floor, uterus, ovaries and vagina, are currently in the preclinical and clinical phases of study. In obstetrics, the area of stem cell transplantation has been largely focused on adult stem cell therapy
Firdos Alam Khan
Imam Abdulrahman Bin Faisal University, Saudi Arabia
Title: Isolation of pluripotent stem cells from an adult human eye

Biography:
Professor Firdos Alam Khan is a Professor, and Chairman, Department of Stem Cell Biology, Institute for Research & Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. Professor Khan received his PhDl degree in Neuroscience from Nagpur University, India. Professor Khan has 24 years of research and teaching experience in various domains of biotechnology. He did his postdoctoral fellowship from Massachusetts Institute of Technology, Cambridge, USA. Perofessor Khan’s research interests are stem cell biology and neuroscience, and he has been working on the neural stem cells understanding their differentiation capabilities with relation to therapeutics and diagnostics aspects. Profess Khan is exploring the role of nanoparticles in cancer cells with therapeutic potentials as well as in the stem cells.
Abstract:
We have investigated whether the adult human cornea-limbal tissue has any self-renewing and multi-lineage differentiation capacities. We report, the identification and isolation of limbal fibroblast-like cells obtained from the adult human corneo-limbal tissue possessing self-renewing capacity and multi-lineage differentiation potential. The cells form cell aggregates or clusters, which express molecular markers, specific for ectoderm, mesoderm and endoderm lineages in vitro. Further, these cells mature into a myriad of cell types including neurons, corneal cells, osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes and pancreatic islet cells. Despite originating from a non-embryonic source, they express Embryonic Stem Cell and other stem cell markers important for maintaining an undifferentiated state. This multi-potential capability, relatively easy isolation and high rate of ex vivo proliferation capacity make these cells a promising therapeutic tool.
Maria Cristina Tanzi
INSTM UdR Polytechnic of Milan, Italy
Title: Polyurethane foams as biomimetic composite scaffolds for bone and osteochondral tissue repair

Biography:
Maria Cristina Tanzi obtained her Master Degree in Chemistry and Pharmaceutics in 1975 with honors and her Specialization Degree in Experimental Pharmacology in 1979 at Milano University. She was Full Professor of Industrial Bioengineering, at the Bioengineering Department, and then at the Chemistry, Materials and Chemical Engineering Department of Politecnico di Milano until March 1st, 2014 when she retired. She was Director of the Laboratory of Biomaterials and co-Director of the Laboratory of Biocompatibility and Cell Culture at Politecnico di Milano. In May 2008 she was nominated member of The International College of Fellows of Biomaterials Science and Engineering.
Abstract:
In the last 20 years, we investigated the design of polyurethane (PU) foams suitable for use as scaffolds in Tissue Engineering [1] and we gained a strong know-how on this line of research. In particular, biocompatible composites with calcium phosphates have been developed and tested for bone regeneration [2-4]. In addition, bio mineralization of the PU foams, carried out by activation of the PU surface with a two steps procedure [5], led to a significant increase of mechanical properties and provided a more suitable surface for rat BMSCs attachment and proliferation. Recently, our research activity was aimed at designing and developing a novel functionally-graded hybrid (FGHY) scaffold with the PU foam representing the load-bearing structure, CaPs with a graded composition the biomimetic component, and pectin gel the cell carrier [6]. Human placenta-derived cells (hPDC) populations encapsulated in pectin gels and injected into the FGHY scaffolds demonstrated the ability to differentiate toward the osteogenic lineage. The ability of these biomimetic hybrid scaffolds to stimulate cell adhesion and proliferation and to support differentiation of hPDCs makes these scaffolds excellent candidates for osteochondral tissue repair.[1] S. Fare, et Al., EUROMAT, Biomaterials, 2001, 6, 1;[2] M.C. Tanzi et Al., J. Appl. Biomater. Biomech.2003, 1, 58; [3] M. Zanetta, et Al., Acta Biomaterialia, 2009, 5, 1126; [4] S. Bertoldi, et Al., J. Mater. Sci: Mater. Med. 2010, 21, 1005; [5] M. Meskinfamet Al., Materials Science and Engineering C, 2018, 82, 130; [6] S. Fare et Al., Proceedings IEEE-EMBS, 2015, 7318717, 1753.
Beatriz de Lucas Moreno
European University of Madrid, Spain
Title: Membrane blebbing is required for mesenchymal precursor migration

Biography:
Beatriz is in the final year of her PhD at European University of Madrid (Spain). She obtained her Degree in Health Biology in 2013 at University of Alcalá and her Master in Molecular Biomedicine in 2014 at Universidad Autónoma de Madrid. She is author of 5 papers in reputed journals.
Abstract:
Mesenchymal precursors (MPs) are present in a great variety of adult tissues and have a variety of properties, such as differentiation and migration, which make them attractive candidates for cell therapy. However, the delivery of the cells is still a major problem thus a better understanding of MP migration characteristics would aid the development of cell delivery protocols. Studying the migration of MPs in vitro, we found the presence of blebs in them. Blebs are cytoskeleton-regulated dynamic structures pressure-driven, as a result of strong actomyosin forces. Not long ago blebs were considered a hallmark of apoptosis, nevertheless their role in cell migration and in other physiologic processes are gaining great importance. Here we report that MPs derived from different tissues present spontaneously dynamic cytoplasmic projections in sub-confluent culture, which appear as a combination of lamellipodia with blebs in the leading edge. Upon initial seeding, however, only bleb structures could be observed. Immunofluorescence revealed the presence of pERM, RhoA and Factin during the blebbing process. Results from migration assays in the presence of blebbistatin, a myosin II inhibitor, showed that bleb formation correlated with migratory capacity, suggesting a functional role for blebs in migration. Bleb formation might be a useful mechanism to improve cell migration in cellular therapy protocols.
Seyedeh Esmat Hosseini
Royan Institute for stem Cell Biology and Technology, Iran
Title: The efficacy of platelet gel derived umbilical cord blood on diabetic foot ulcers: a double -blind randomized clinical trial

Biography:
Esmat Hosseini is a PhD student in nursing in Tehran university and graduate student as Master of Science in School of Nursing Shahid Sadoughi Yazd University of Medical Sciences from Iran. Regarding my scientific background, I would like to inform you that I have an associate Degree in nurse anesthesia and Bs in Nursing and Master of Science in Critical Care Nursing. About 10 years I worked in operation room (as a nurse of anesthesia) and intensives ward. I was supervisor Royan Institute of Cell Therapy center. Now I am researcher in Royan Institute. I have published more than 10 papers. Also I am reviewer journal of client care.
Abstract:
Type 2 diabetes is one of the most prevalent diseases throughout the world. The foot ulcers are severe complications of this disease. Foot ulcers induce the high rate of morbidity, impair quality of life and bring about extreme costs to health service providers and give rise to waste of time. Recently, platelet-rich plasma (PRP) and platelet gel (PG) have been used for the treatment of chronic wounds. In the present randomized, double -blind, placebo-controlled study, platelet gel derived from umbilical cord blood (UCB) was used to heal the diabetic foot. The patients were randomly divided into three groups, under the categories of Platelet gel (PG), platelet-poor plasma (PPP) and lubricant gel (placebo) (ratio 1:1:1). The processes of gels application were launched for the subject of each group twice per week with 3-4 day interval. This mechanism protracted for eight weeks. After completion of 8 weeks, the patients were followed up after two weeks and then continued for three months with one -month interval. 30 patients underwent statistical analysis. Except for diastolic blood pressure which was significant between groups, there were no statistically significant differences in patients’ baseline demographics. No significant differences were detected between groups at baseline of wounds (P = 0.09). The results revealed that there is no statistically significant interaction among three groups during follow- up time. The present study provides evidence that there are no significant differences in the size of wound among PG, PPP, and placebo group.
Afshin Tadrisi
Shahid Beheshti University of Medical Sciences, Iran
Title: Effect nursing education on anxiety and pain in patients undergoing stem cell therapy - a randomized clinical trial
Biography:
Afshin Tadrisi is pursuing Master of Science in School of Nursing, Shahid Beheshti University of Medical Sciences from Iran. Regarding Afshin Tadrisi’s scientific background, Afshin Tadrisi has obtained Master of Science in Geriatric Nursing and worked in emergency and intensives ward for about 14 years. Afshin Tadrisi was a Supervisor at an emergency center. Also, Afshin Tadrisi was a Researcher in Shahid Beheshti University.
Abstract:
Bone Marrow Aspiration (BMA) is one of the methods for diagnosis and treatment of various diseases, that now day it is widely use in regenerative medicine. Although this Procedure in adults is usually performed by using local anesthesia, it is associated with anxiety and pain. The purpose of this study is to research into the effect of Deep Breathing Technique (DBT) on patients who have undergone BMA for appeasement of pain and reduction of anxiety. This study was a parallel randomized clinical trial. 60 patients who underwent BMA were randomly divided into two groups. Intervention group received DBT training and control group did not go through any training program. To measure the scope of anxiety and severity of pain, Spiel Berger State Anxiety Inventory (SAI) and Visual Analogue Scale (VAS) were used respectively. The Anxiety before and pain after BMA were evaluated in two groups. Comparison of anxiety and pain variables in study groups revealed that the mean score of anxiety and VAS average in the intervention group have been lower than that of the control group and this difference was significant (P = 0.018 and P < 0.001 respectively). Comparison of vital signs before and after DBT showed reduced the vital signs after intervention. However, no significant change was observed in control group. DBT is an effective technique to reduce anxiety and relieve pain in BMA candidate.