7th Annual Conference on Stem Cell and Regenerative Medicine Aug 04-05, 2016 Manchester , UK

Biography:

John Yu is Distinguished Chair Professor/Director, Institute of Stem Cell/Translational Cancer Research, CGMH. He is also Distinguished Visiting Research Fellow at Institute of Cellular & Organismic Biology, Academia Sinica, and was the Director for the same Institute (2002-2009). He is the founding President for Taiwan Society for Stem Cell Research. Dr. Yu was elected to serve in many ISSCR Committees USA, the Steering Committee of Asia-Pacific Stem Cell Network, and advisor for Stem Cell Biology, Kumamoto Univ. He was Director of Exp. Hematology (1998-2002) at Scripps Research Institute, USA. He received an Established Investigatorship Award from American Heart Assoc. and many other awards.

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Prof. Jun HU completed his MD from Xiangya Medical College of Zhongnan University and postdoctoral studies from South China Normal University. He is the director of the department of orthopaedics, in Shantou University Medical College. His research team is interested in the development of innovative approaches for enhancing bone fracture healing and cartilage repair. He has published a number of original papers in reputed journals, including Nanomedicine, the Journal of Biological Chemistry, Scientific Reports, and Journal of Biomedical Optics. He also serves as a nominated reviewer for NSFC proposals in China. 

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Extracorporeal shockwave (ESW) has been shown of great potential in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but it is unknown whether this osteogenic promotion effect can also be achieved in other MSCs (i.e., tendon-derived stem cells (TDSCs) and adipose-derived stem cells (ADSCs)). In the current study, we aimed not only to compare the osteogenic effects of BMSCs induced by ESW to those of TDSCs and ADSCs; but also to investigate the underlying mechanisms. We show here that ESW (0.16 mj/mm2) significantly promoted the osteogenic differentiation in all the tested types of MSCs, accompanied with the downregulation of miR-138, but the activation of FAK, ERK1/2, and RUNX2. The enhancement of osteogenesis in these MSCs was consistently abolished when the cells were pretreated with one of the following conditions: overexpression of miR-138, FAK knockdown using specific siRNA, and U0126, implying that all of these elements are indispensable for mediating the effect of ESW. In addition, our study provides converging genetic and molecular evidence that the miR-138-FAK-ERK1/2-RUNX2 machinery can be generally activated in ESW-preconditioned MSCs. More importantly, this machinery has also been confirmed by our in vivo experiments, including nude mice spontaneous implantation model and rat femur close fracture model. All these findings suggest that ESW may be a promising therapeutic strategy for the enhancement of osteogenesis of MSCs, regardless of their origins.

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Mohammad Ghasemzadeh-Hasankolaei has graduated in Veterinary Medicine in 2005 and joined PhD program in Veterinary Reproductive Sciences in 2006; simultaneously, he started his studies on stem cells at Royan Institute, Iran. He has published a number of papers in the field of stem cells and germ cells. He is working as an Assistant Professor at Babol University of Medical Sciences, Iran since 3 years. He has founded the “Stem Cells Research Lab.” in the “Infertility and Reproductive Health Research Center” of the university in 2013.

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Here we describe our three different research experiences in the field of generation of male germ cells (GCs) from mesenchymal stem cells (MSCs). In the first research, ram bone marrow (BM)-MSCs, were induced to differentiate into male GCs by different methods; treatment with different concentrations of retinoic acid (RA) for 14 and 21 days, 100 ng/ml BMP4 and BMP8b and also 10 ng/ml TGFb1, all for 21 days (all in separate groups). Results showed that, the most efficient methods were 21 days treatment with 10 µM RA and 10 ng/ml TGFb1. Transplantation of the induced GCs into testes revealed that, after 2 months, although, a number of cells could home in the seminiferous tubules, they could not differentiate farther from spermatogonia state. In the second study, we evaluated the potency of intact autologous rat BM-MSCs for regeneration of testis germinal epithelium after induction of infertility with busulfan injection. Evaluations after 4, 6 and 8 weeks showed that a number of BM-MSCs was located in the germinal epithelium and expressed spermatogonia specific markers. In our third study, we treated mouse amniotic membrane MSCs with 50 ng/ml BMP4 for 5 days and immediately with 10 µM RA for 12 days. Eventually, there were some germ-like cells in the culture. Finally, although, in all of our experiments, a number of treated cells differentiated into the GCs, the efficiency was very poor. It seems it is still too soon to have developed functional GCs from MSCs in vitro.

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Huanhuan Joyce Chen has received her PhD degree in Biomedical Engineering at Cornell University. She is currently a Postdoctoral Associate with Dr. Harold Varmus at Weill Cornell Medicine. She has published more than 15 papers in reputed journals such as Nature Biotech and Cell Stem Cell and received awards including National Science Foundation Graduate Research Fellowship and National Cancer Institute Physical Sciences in Oncology Young Investigator Award.

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Current cancer research hinges on developing models that accurately recapitulate cancer disease phenotypes. Though animal models are very useful tools, the major limitation stems from species variation that animal models can be considerable different to human cancers and fail to faithfully recapitulate human conditions. To address this issue, we engineered an ex vivo colon cancer models by recellularization of human native matrix with human colonic stem cells derived cell resources. We followed to demonstrate the significance of the organotypic human-originated model in studying cancer biology by combining transposon-based mutagenesis. Another problem rises from the availability of tissue-specific cell types representative of clinical disease features, especially in the lung cancer types with the scarcity of primary tumors for generation of cell lines. Here, I will also describe my current efforts to synthesize cellular engineering, single-cell methods with human pluripotent stem cell technology for lung cancer modeling.

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Background: Responses to neo adjuvant chemotherapy (NAC) are used as surrogates to evaluate systemic response in patients. 85% of patients have residual disease (RD) implying some degree of treatment resistance. We hypothesize that the frequencies and mutation status of breast cancer stem cells (BCSC) in the tumor will correlate with having RD after NAC.

Methods: Fresh surgical specimens collected from invasive ductal carcinomas (IDC) before and after NAC. BCSC were counted and mutations identified by array platform, assessing 2800 mutations in 50 tumor suppressor and oncogenes. Changes in tumor size, receptor status, BCSC frequencies and mutation identification were compared between treatment naïve IDC and IDC after NAC.
Results: There were 39 women with IDC, of which 15 received NAC. 
Treatment naive and NAC treatment groups had similar clinical characteristics except for an increase of ER^-/PR^- tumors in the latter (8% vs. 40%, p=0.04). Mean sizes of naïve tumors were 3.0 cm and those receiving NAC were 2.6 cm. Mean size of RD was 3.4 cm. The frequencies of PIK and TP53 oncogene mutations were 32% and 3.6%, respectively, in treatment naive tumors compared to 36.4 % and 36.4%  in RD (p=0.016). Specific BCSCs harboring these mutations had a 3.7 fold higher frequency in RD among both ER/PR positive and negative tumors (p<0.0004). 
Conclusions: Following NAC, breast cancer RD contained higher frequencies of BCSCs carrying aggressive cancer mutations compared to tumors prior to NAC or tumors with no RD. These cell populations are not only resistant but may be increased by NAC. RD molecular assessment provides opportunities to evaluate the mechanisms of response/resistance to NAC, as well as to direct further therapies. 

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Naglaa Kamal Idriss has completed her PhD from Birmingham University and Postdoctoral studies from Southampton School of Medicine. She is the Member of International Society for Stem Cell Research (ISSCR) and European Society of Cardiology, ESC working group on Coronary pathophysiology and microcirculation. She has published more than 15 papers in reputed journals.

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Zhang is an Associate Professor in the University of Texas Medical School at Houston. He received his Ph.D. from MD Anderson Cancer Center and postdoctoral training from Howard Hughes Medical Institute, Baylor College of Medicine. His research focuses on epigenetic mechanism of Na+ and water homeostasis, with a special emphasis on histone H3 K79 methyltransferase Dot1l and the epithelial Na+ channel. He created Af17 knockout and Dot1l conditional knockout mice. Recently, he began to study biomarkers and stem cells in kidney injury and repair. He has published >40 peer-reviewed papers and received funding from NIH, AHA and ASN.   

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Connecting tubule (CNT) interconnects nephron and collecting duct (CD), which arise from kidney mesenchyme and the branching ureteric epithelium, respectively, to generate the functional tubular networks. CNT is thought as a product of reciprocal induction between the adjoining segments. The identity of the ureteric progenitors contributing to CNT remains virtually unknown. Recently, we reported that Aqp2-expressing cells with disrupted Dot1l give rise to principal cells (PC) and intercalated cells (IC). However, whether such derivation occurs naturally and whether Aqp2⁺ progenitors contribute to CNT has never been addressed. Here, we generate a new mouse model (R^AC) in which Aqp2 lineage is genetically traced by red fluorescence protein. With high-resolution image analysis, we demonstrate that Aqp2⁺ progenitors naturally give rise to not only PC and IC, but also several types of CNT cells. CNT can be divided into three molecularly distinct segments. These segments contain CNT/DCT transitional cells, which originate from Aqp2⁺ progenitors, but gain expression of NCC, a well-established DCT marker. Our study highlights the molecular identity and the origin of novel and distinct CNT segments and discovers Aqp2⁺ progenitors as one of the origins of various types of cells not only in the CD but also in the CNT. Therefore, our study reports a novel mouse model that faithfully traces Aqp2 lineage and demonstrates a novel function of Aqp2⁺ progenitors in CNT formation. The discovery of the CNT segments and Aqp2⁺ progenitors may facilitate their isolation and functional evaluation

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Dennis M Lox has attended the University of Arizona where he was Phi Beta Kappa. He has received his Medical degree at the Texas Tech University Health Sciences Center and his Residency Training in Physical Medicine and Rehabilitation at the University of Texas Health Sciences Center at San Antonio. He has maintained a private practice in the Tampa Bay, Florida and presently in Beverly Hills, California. He specializes in musculoskeletal disorders, sports medicine and regenerative medicine. He has edited two medical textbooks, written eight textbook chapters and scientific publications. He has also lectured extensively in the areas of regenerative and sports medicine.

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The use of regenerative medicine applications such as stem cell therapies may have a common thread in the management of sports medicine patients. Trauma is a precipitating event in sports for the development of early onset osteoarthritis, as well as Avascular Necrosis (AVN). An understanding of the underlying pathophysiological processes involved in both post traumatic osteoarthritis and Avascular Necrosis (AVN) may direct treatment towards the use of regenerative medicine and stem cells. The progression of post traumatic osteoarthritis and AVN after sports injuries may direct early treatment methodologies toward a regenerative model, rather than a time sensitive progressive degenerative cascade. Case representations will demonstrate a parallel tract for the investigation and management of sports medicine patients who are at risk for or developed post-traumatic osteoarthritis and those with Avascular Necrosis (AVN).

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Yechiel Elkabetz has earned his BSc, MSc and PhD in Cell Biology from Tel Aviv University. He has started his investigation of human pluripotent stem cells (PSCs) and neural stem cells (NSCs) in 2004 at Lorenz Studer group at Sloan-Kettering Institute, NY. His study at the Sloan led to the isolation of a novel early type of NSCs termed rosette neural stem cells, which became a platform for understanding early neural specification events in vitro. In 2009, he established his lab at Tel Aviv University

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Modeling key cell fate decisions and heterogeneity during the establishment and ontogeny of cortical neural progenitors is fundamental for revealing origin of diverse lineages, identifying molecular forces regulating distinct potencies and developing strategies for generating homogeneous cortical neural stem cell (NSC) populations for regenerative medicine. Here we report our recent progress in developing such approaches and their implications. We isolated consecutive neural progenitors derived from human pluripotent stem cells (PSCs) differentiated along cortical development based on their notch activation state. We first isolated notch active CNS neuroepithelial cells exhibiting high proliferation and broad potential. These successively yield early and mid cerebral neurogenic radial glia followed by gliogenic radial glia, together recapitulating hallmarks of NSC ontogeny, cortical lamination and glial transformation in notch dependent manner. We used isolated stages as modules to identify forces driving cell fate transitions. We employed gene expression analysis and epigenetic profiling combined with computational approaches to infer key regulators progressively remodeling the epigenetic landscape and followed by shRNA functional validation. This allowed uncovering a core gene regulatory network of stably expressed transcription factors that dynamically interacts with stage specific factors to regulate cortical NSC fate transition. We further used these data to identify dynamics of pathway activation during this process and based on these we developed a streamlined and robust protocol for efficient cortical cell fate conversion from naive and primed PSCs using small molecules. We also used this method to efficiently develop cerebral organoids that are homogeneous for cortical regional fate and stem cell state. To exemplify the utility of the new protocol to model disease, we generated a microcephaly PSC line by introducing an autosomal recessive microcephaly mutation. We observed dramatic differences in microcephaly vs. WT organoids that were only apparent when specifically derived by our new protocol. We further identified abnormal cortical layer lamination and precocious differentiation in microcephaly organoids accompanied by cytoarchitectural and cellular defects, hence leading to a novel delineation of early pathology of microcephaly in cortical NSCs.

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Hazem Barmada is a Cardiovascular and Thoracic Surgeon. He was graduated from St. Andrews and Manchester Universities in 1971 and 1974, respectively. He was active in martial arts in Britain from 1968 to 1984 and was a Medical Officer to the Martial Arts Commission and other major karate organizations in GB from 1974 to 1984. He is a Fellow of the Royal College of Surgeons of Edinburgh in General and Cardiothoracic Surgery, the intercollegiate British Boards in Cardiothoracic Surgery and the Royal Society of Medicine in London and is also a Member of the Society of Thoracic Surgeons and American College of Phlebology. He has two patents and published a number of papers. His interests include regenerative medicine and stem cell research, sports injuries and venous and lymphatic disease.

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Stromal vascular fraction (SVF) was first isolated from adipose tissue around 1970, but it was not until early this century that its potential in providing regenerative cells for treatment of various medical conditions was realized. SVF has proved very effective in helping manage many hitherto difficult or untreatable conditions, including severe degenerative joint disease (DJD), medically. Nonetheless, it has not been effective in every case, especially in the more severe cases of DJD. Extracorporeal Pulse Activation Technology (EPAT), Alias Dictus Shock or Pressure Wave Therapy (ESWT), is a non-invasive technology platform of Storz Medical that employs acoustic pressure waves to affect a mechanico-transduction response at the cellular level, which leads to cell activation, improved metabolism, angiogenesis, neovascularization and improved healing. This has been used as a stand-alone modality for treating various musculoskeletal conditions in Germany over the past twenty years. In four patients with severe DJD who have either refused surgery or had undergone multiple unsuccessful surgeries, we found the addition of EPAT to the deployment of SVF intravenously and locally, highly effective in decreasing pain, reducing stiffness and increasing functionality.

Biography:

Serban San-Marina has completed his undergraduate and graduate studies at the University of Toronto, Medical studies at the Carol Davila School of Medicine and holds a PhD in Biology from York University. He has completed his Post-doctoral fellowships at Penn State in T-cell Immunobiology and at the Ontario Cancer Institute in Leukemia Transcription Factor Research. In 2006, he has co-founded Biostatistix for repurposed drug discovery. He has joined the Mayo Clinic in 2013 where his interests are in small molecule-directed stem cell reprogramming for regenerative medicine.

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In spite of extraordinary recent progress in stem cell research, the replacement of tissues of the human body is currently unachievable with existing protocols. Furthermore, the need to replace damaged tissue and organs compel the development of technologies poised for early adoption that are sufficiently flexible to accommodate a personalized/precision approach. The current innovation deficit is due in part to limited choices of starting materials, incomplete knowledge of the factors affecting lineage commitments and limitations in gene delivery systems. To enable faster ‘go/no go’ testing of new hypotheses, there is a need to increase reprogramming efficiency. We are addressing the issue or restoring organ functionality using small molecule-assisted protein reprogramming and stress-resistant pluripotent stem cells. To enable efficient reprogramming, small molecule process boosters are identified by zebrafish (zf)-assisted screening of compound libraries, including FDA-approved drugs that can be rapidly re-purposed. To illustrate the transforming potential of this technology we have selected as an end point, the regeneration of hair-like cells in the cochlea.

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Jane Lebkowski has been actively involved in the development of cell and gene therapies since 1986 and is currently a Chief Scientific Officer and President of R&D at Asterias Biotherapeutics Inc, where she is responsible for all preclinical and product development of Asterias’ products. From 1998 to 2012, she was a Senior Vice President of Regenerative Medicine and Chief Scientific Officer at Geron Corporation. Before joining to Geron, she was a Vice President of R&D at Applied Immune Sciences. Following acquisition of Applied Immune Sciences by Rhone Poulenc Rorer (currently Sanofi), she also served as a Vice President of Discovery Research. She has received her PhD in Biochemistry from Princeton University in 1982 and completed her Postdoctoral Fellowship at the Department of Genetics, Stanford University in 1986. She has published over 70 peer reviewed papers and has 13 issued US patents. She is on the Board of Directors of the American Society for Gene and Cell Therapy and also served as an Industry Representative to FDA’s Office of Cell, Tissue and Gene Therapy Advisory Board.

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Human Embryonic Stem Cells (hESCs) can proliferate indefinitely yet, upon appropriate cues, differentiate into all somatic cell lineages. These two properties of hESCs enable the development of hESC-derived therapeutic cell populations which can be batch manufactured in central manufacturing facilities, cryopreserved and distributed for “on demand” use at healthcare providers. Protocols have been developed to differentiate hESCs into neural, cardiomyocyte, hepatocyte, islet, osteoblast, chondrocyte and hematopoietic cell populations which have been shown to be functional in either in vitro or in vivo animal models of human disease. Our group has established protocols to produce oligodendrocyte progenitors that upon transplantation into animals with spinal cord injuries can remyelinate denuded axons induce axonal sprouting and improve locomotor activity. Extensive preclinical studies have been completed to examine the activity, bio-distribution, dosing, delivery and potential toxicity and tumorigenicity of the http://stemcell-regenerativemedicine.conferenceseries.com/http://stemcell-regenerativemedicine.conferenceseries.com/ progenitors. The safety of these cells is now being tested in the clinic in subjects with complete spinal cord injuries. In addition our team has developed methods to produce dendritic cells from hESCs that have the antigen processing and presentation functionality to stimulate immune responses. In collaboration with Cancer Research UK, Asterias is preparing for a clinical trial using these hESC derived dendritic cells as a cancer immunotherapy in non-small cell lung carcinoma in the neoadjuvant setting Human Embryonic Stem Cells (hESCs) can proliferate indefinitely yet, upon appropriate cues, differentiate into all somatic cell lineages. These two properties of hESCs enable the development of hESC-derived therapeutic cell populations which can be batch manufactured in central manufacturing facilities, cryopreserved and distributed for “on demand” use at healthcare providers. Protocols have been developed to differentiate hESCs into neural, cardiomyocyte, hepatocyte, islet, osteoblast, chondrocyte and hematopoietic cell populations which have been shown to be functional in either in vitro or in vivo animal models of human disease. Our group has established protocols to produce oligodendrocyte progenitors that upon transplantation into animals with spinal cord injuries can remyelinate denuded axons induce axonal sprouting and improve locomotor activity. Extensive preclinical studies have been completed to examine the activity, bio-distribution, dosing, delivery and potential toxicity and tumorigenicity of the oligodendrocyte progenitors. The safety of these cells is now being tested in the clinic in subjects with complete spinal cord injuries. In addition our team has developed methods to produce dendritic cells from hESCs that have the antigen processing and presentation functionality to stimulate immune responses. In collaboration with Cancer Research UK, Asterias is preparing for a clinical trial using these hESC derived dendritic cells as a cancer immunotherapy in non-small cell lung carcinoma in the neoadjuvant setting

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Raphael Gorodetsky is the Head of the Laboratory of Biotechnology and Radiobiology at the Sharett Institute at Hadassah Medical Center. He studies various aspects of biotechnology, including radiobiology and tissue regeneration, development of new fibrin related bio-matrices and cell adhesion properties of a new family of cell penetrating peptides homologous to sequences on the C-termini of fibrinogen. His current focus is on cell based therapies with isolated potent secreting cells, such as isolated placental derived stromal cells for regenerative medicine and their trophic effect for mitigation of lethal high dose ionizing radiation syndrome inducing bone marrow regeneration and for treating other degenerative conditions.

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We have developed highly efficient protocols for the isolation and expansion of vast numbers of potent stromal cell (hPSC) populations from selected layers of full term human placentas. The isolated hPSC could be expanded to high cell numbers, to be stored for further use. IM delivered hPSC were well tolerated as allogeneic or trans-species implants and resided with minimal rejection in the implanted muscle for many weeks before their full clearance. IM administration of hPSC in a mouse model of lethal acute radiation syndrome (ARS) following irradiation by ~8Gy dramatically elevated the survival of the mice form as low as ~25-30% to ~100% with enhancement of regeneration of the hematopoietic system. The hPSC activation by host systemic stress signals resulted in the secretion of a wide range of human-derived cytokines and growth factors into the circulation with boosting of bone marrow and spleen derived hematopoietic progenitor cells. This shed light on the mechanism of action of the potent hPSC. Our results suggest that these cells could be used as an effective allogeneic cell therapy for severely depleted hematopoietic system aside from mitigating ARS. IM treatment with hPSC also showed very promising preliminary results with other disease models, such as inflammatory bowel disease (IBD) and progressive phases of the EAE model of multiple sclerosis (MS). These results suggest that the hPSC may be highly effective as allogeneic cell treatment of different degenerative and autoimmune diseases by boosting regenerative processes, modulating inflammation and stimulating stem cells proliferation in damaged tissues.

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Since 2006, Andreas Kurtz is Head of the Laboratory for Stem Cell Research and Knowledge Management at the Berlin-Brandenburg Center for Regenerative Therapies, Berlin (Germany). He also holds a professorship at Seoul National University since 2008. Before he served as director of the German stem cell authority at the Robert-Koch-Institute. His research interest is the application of stem cells for therapy and the development of suitable in vitro models to assess their mode  of action.. In addition, he coordinates the human pluripotent stem cell registry (hPScreg), an international data resource for iPSC and hESC.

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Chronic kidney diseases have worldwide an increasing prevalence (8-16%) and develop frequently in chronic renal failure requiring dialysis. Kidney transplantation has emerged as the “gold standard” therapy for end-stage renal failure as it improves both quality of life and survival. Despite the progress in short-term graft survival that is closely associated with the impressive reduction of acute rejections within the first year, long-term graft and patient survival remain almost unchanged and unsatisfactory. Incomplete control of chronic allograft injury but particularly the adverse effects of life-long required immunosuppression (graft toxicity, diabetes, cardio-vascular events, infections, tumors) continue to challenge the long-term success and cause high direct and indirect (management of adverse effects) costs (about 0.5-1.0 Million Euros/10 years). Consequently, there is a high medical need to develop new protocols that allow minimization or even weaning off chronic immunosuppression. The increased net-immunosuppression introduced during last decades can better control the undesired alloreactivity even in patients at risk but it also targets physiologic counter-regulatory processes that protect to inflammation/immune reactivity. Therefore, minimizing chronic immunosuppression is only feasible if these endogenous counter-regulatory mechanisms are spared or even supported. Recently, we could demonstrate in a clinically relevant advanced rat kidney transplantation model that even under those challenging conditions the adoptive transfer of regulatory T cells (Treg) could reshape alloimmunity to “operational tolerance”. In the process of translating these promising data into patients´ treatment we faced several challenges. We developed a robust GMP-manufacturing process for isolation, activation and expansion of human Treg from just 40-50 ml blood as source. The Treg can be expanded about 1,000 fold without clonal bias, as shown by TCR-repertoire analyses using Next Generation Sequencing and without loss of regulatory function. We recently started a dose-escalating phase I/IIa clinical first-in-man study with our Treg cell product and reached already the highest target dose without any safety issue. The modulation of endogenous immunological control mechanisms by Treg might be a novel approach to improve long-term allograft survival but also to control other undesired process to support endogenous regeneration. To address the shortage of donor organs, it would be useful to prolong the survival of injured kidneys. Reconstitution of injured kidneys by application of progenitor cells was not feasible so far because of lacking resources for those cells. The availability of human iPS technology opens new opportunities. However, the kidney is a very complex organ consisting of about 26 cell types embedded into matrix. Few groups, including ours are able to generate renal organoids from human iPS now. We could further improve the method and can efficiently generate renal precursor cells within 6 days and terminally differentiated kidney cells in 2-D culture within 14 days. The progress in this field makes the in vitro generation of human renal cells for disease modeling but also for putative therapeutic approaches a realistic option.

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Decio Basso has earned his Medical degree in 1982 from the Federal University Santa Catarina (UFSC), at Florianopolis, Brazil. He then attended PUC-Pontifical Catholic University of Rio Grande do Sul, Brazil to pursue a specialization Medical Degree Geriatric and Gerontology in 1990; after graduating, he was for an internship continuing education at Harvard Medical School in Boston, USA. He has been an integral part of medical staff at The Department of Immunology at the University of British Columbia, Canada. He is serving as a Professor at UPE (Universidad Privada Del Este, Paraguay). He is the Founder of the Gerobasso Medical Research Center; a medical research organization.

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The Sclerosis Lateral Amyotrophic (ALS) also known as "Lou Gehrig's disease" is a progressive neurodegenerative disease that affects the nerve cells of the brain and spinal cord; the motor neurons of the brain to the spinal cord and the spinal cord to the muscles throughout the body. When the motor neurons die, the brain loses the ability to initiate and control muscle movement. Because of the progressive effect on the action of voluntary muscles, patients in the final stages of the disease may become totally paralyzed. A-myo-trophic comes from the Greek. "A" means no or missing. "Mio" refers to muscle and "trophic" means food: "No power to the muscles." When a muscle is not fed, it "atrophies" or wears. "Lateral" identifies areas of the spine where the parts of the nerve cells that control muscle and signals are located. As this area degenerates, produces hardening or scarring ("sclerosis") in the region. In the more advanced stages of the disease, they are observed: Decreased respiratory, muscle strength, progressive loss of body weight, loss of muscle mass and dysphagia. The (ALS) is considered the most devastating disease characteristics among all neurodegeneration. In this clinical case, the patient arrived in the clinic diagnosed as ALS with electroneuromyography report, requested by the neurologist confirmed, affecting inferior motor neuron. Treatment proposed with stem cell implant (mesenchymal autologous). The implant stem cells, through the release of growth factors act to prevent the death of motor neurons. They feed the motor neurons or make them healthier, slow the degenerative process.

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Haiko Pas was graduated from Leiden University Medical Centre. He is currently working as a Senior House Officer for the Department of Pulmonology, Spaarne Gasthuis Haarlem. He has previously worked in the Department of Cardiology, Alrijne Hospital Leiden. He has also worked as a Researcher for the Sports Physician group, Onze Lieve Vrouw Gasthuis location West, Amsterdam.

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Introduction & Aim: Stem cell treatment for knee osteoarthritis is emerging as a new treatment modality and we aimed to review its effect.

Methods: Published and non-published, (non-) randomized controlled trials were searched in various databases and trial registers. Risk of bias appraisal was performed using the Cochrane Risk of Bias Tool. Levels of evidence according to the Oxford Centre for Evidence Based Medicine were used to express the strength of evidence. A descriptive synthesis was performed as meta-analysis was not possible.

Results: Six trials with a total of 155 stem cell treated patients were found. All trials were deemed to be at high risk of bias and they were graded down to a Level 3-4 of evidence. Autologous adipose derived mesenchymal stem cells, autologous and allogenic bone marrow derived mesenchymal stem cells and autologus peripheral blood stem cells were used. Concomitant surgery was performed in all but one trial. Due to clinical heterogeneity, no meta-analysis was possible. Five out of six trials found favorable results for functional, radiological or histological outcomes compared to controls. No serious adverse events were reported.

Conclusion: Studies investigating the effect of stem cell therapy for patients with knee osteoarthritis show a trend in favor of stem cell therapy (level 3-4 of evidence). However, due to a high risk of bias we deem that there is no proven efficacy for stem cell therapy in patients with knee osteoarthritis. Therefore, we do not recommend its use in practice yet.

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Nilanjana Maulik has completed her PhD in 1990 from University of Calcutta, India. She has joined the Department of Surgery at University of Connecticut, School of Medicine, USA as a Post-doctoral Fellow in 1991. After completing Post-doctoral Fellowship, she joined the Faculty of the University of Connecticut, School of Medicine, Department of Surgery where she currently serves as a Tenured Professor. She is the Director of the Molecular Cardiology and Angiogenesis Laboratory. She serves several NIH study sections and Editorial Board Member of several prestigious journals. She is the Editor-In-Chief of Molecular Biology Report, Springer. She has published more than 190 articles, 35 book chapters and three books (CRC and Springer press) related to cardiovascular disease and epigenetics.

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Implantation of mesenchymal stem cells (MSC) is becoming an exciting new method for promoting repair of infarcted myocardium. In this study, we use an adenoviral vector encoding Thioredoxin-1 (Ad.Trx1) to genetically modify MSCs prior to implantation. Trx-1 has been established as a redox regulator of growth and transcription-factors as well as a cofactor. It has also been shown to be a potential antioxidant. We wanted to study whether Trx-1 engineered MSCs are capable of improving cardiac function and angiogenesis in a rat myocardial infarction (MI) model. In order to do so, rat MSCs were cultured and divided into three groups: MSC, MSC-LacZ and MSC-Trx1. The cells were assayed for survivability, proliferation and differentiation potential. Additionally, rats were randomized into control Sham (CS), control MI (CMI), MSC-LacZMI (MLZMI) and MSC-Trx1MI (MTRXMI) groups (n=20 per group). MI was induced by permanent occlusion of the LAD immediately after which MSCs preconditioned with either Ad.LacZ or Ad.Trx1 were administered at 4 peri-infarct areas. We observed increased proliferation of MSC-Trx1 cells in vitro that maintained pleuripotency to divide into cardiomyocytes, smooth muscle and endothelial cells. In treated rats, capillary density increased in the MTRXMI group when compared to the both the CMI and MLZMI groups. Western blot analysis showed increased expression of VEGF, HO-1 and CXCR4 and decreased expression of TXNIP in the MTRXMI group. Increased intercellular connections, measured by Cx-43 expression, were seen in the treatment group. Echocardiography showed improved ejection fractions and fractional shortening in Trx-1 treated mice when compared to LacZ and control mice. Additionally, picro-sirus red staining showed Trx-1 treated mice had decreased levels of fibrosis in the myocardium. Trx-1 pretreated MSCs provide protection against myocardial injury via induction of VEGF expression, promotion of neovascularization, reducing fibrosis and increasing functional recovery. Ischemic damage cause by decreased blood flow may be reversed in various cardiovascular diseases by treatment with MSCs preconditioned with Trx-1. The long term clinical management of illnesses, such as MI or peripheral vascular disease, may benefit from the angiogenic properties of Trx-1.

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Sasikanth Adigopula has completed his training at University of California at Los Angeles and Stanford University. Currently he serves as an Assistant Professor in the Division of Cardiology at Loma Linda University and is the Director of Heart Failure at Regional Medical Center. He has received many awards, recognition and support for his research work. His research interest includes stem cell therapy in heart failure and clinical outcomes in advanced heart failure. His work has been published in NEJM, AHJ, AJC, JASE, JACC, Circulation and IJCVI. He currently serves on the Editorial Board of many peer-reviewed medical journals.

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The human heart has limited regenerative capacity. In patients with Cardiomyopathy both adult stem cells (ASCs) and human pluripotent stem cells (hPSCs) have the potential to facilitate development of cell-based therapies. However, stem cell-based therapies have been limited by numerous challenges, including the proarrhythmic nature of stem cell-derived cardiac grafts. This is from differences in electrophysiologic maturity, gap junction isotypes, cell orientation and wave propagation between graft and host myocardium. On injury, the normal architecture is disrupted and cardiomyocytes are replaced by scar tissue and proliferating fibroblasts, which in turn result in compromise of the structural integrity and adverse remodeling of the heart. These structural changes caused anisotropy, which provide substrates for reentrant arrhythmias. In addition, the action potential duration prolongation potentially produced early after depolarizations or delayed after depolarizations. The key mechanisms leading to arrhythmias in stem cell therapy are lack of electromechanical integration, transplantation of non-cardiomyocyte derivatives, local injury and edema, nerve sprouting, route of cell delivery with intramyocardial being more arrhythmogenic than retrograde intracoronary, immunologic mechanisms leading to rejection and inflammation and graft automaticity. Attempts to introduce exogenous cells for regenerative purposes should consider the hostile environment, the lack of normal myocardial structure and the potential for the introduction of cells in a microenvironment in which normal cardiomyocytes fibers are replaced by scar. Newer delivery systems including cell-seeded patches and scaffold-free cell sheets reduced arrhythmias. Cell coupling and engraftment are also important to reduce risk of reentrant pathways and automaticity, which serve as a nidus for arrhythmia.

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Hongman Wang is a Doctoral Supervisor, Director of Center for Health and Social Development at Peking University Health Science Center. She has conducted extensive research within the field of medical sociology such as development of medical devices industry, medical insurance and medical education. She has published more than 130 papers in reputed journals.

Abstract:

This article analyzes and summarizes issues of intellectual property involved in animal derived regenerative, implantable medical devices (ADRIMD) in order to better understand global trends in patent applications and disclosures, the legal status of patent families (i.e., sets of patents filed in various countries to protect a single invention) and International Patent Classification topics such as main assignee and core expertise. Analysis of research trends will enhance and inform the decision making capacity of researchers, investors, government regulators and other stake holders as they undertake to develop, deploy, invest in or regulate ADRIMD.

Biography:

Dean Nizetic has become one of the leading researchers and opinion-makers in molecular research into Down Syndrome (DS), in particular its relation to stem cell pathology, ageing and cancer. He has recently generated isogenic induced Pluripotent Stem Cells (iPSC) by re-programming the skin fibroblasts from an adult individual with mosaic DS and then cloning separately the genetically identical T21 and euploid (D21) iPSC lines. He is currently leading the Ipsc-cellular modeling stream within the LonDownS consortium. From February 2014, he is a Professor of Molecular Medicine at Lee Kong Chian School of Medicine, Singapore.

Abstract:

Down Syndrome (DS) is the most common genetic cause of intellectual disability and is associated with an increased risk of Alzheimer’s disease (AD). The LonDownS consortium aims to draw correlations between dementia, cognitive defects, mouse models and genetics with in vitro defects in neurons derived from DS induced pluripotent stem cells (iPSCs). For iPSCs, our strategies are: (1) Isogenic iPSC DS models, (2) iPSCs from dupAPP and (3) iPSCs generated from adults and infants, at extremes of the DS spectrum for intensity of pathology. For (1); we developed an integration-free isogenic DS iPSC model by using fibroblasts of an adult with constitutional mosaicism for DS that reproduce several cellular pathologies, including increased β-amyloid, mitochondrial abnormalities and an increase in DNA double strand breaks indicating accelerated ageing. 3D cerebral organoids differentiated from isogenic iPSCs were found to recapitulate aspects of human brain structure and layering. As for (2); iPSCs have been generated from one dupAPP patient and for (3); to maximize consent, hair follicles and/or blood samples are collected from participants clinically stratified for cognitive ability and dementia. So far, >400 DS adults have been recruited with >120 keratinocyte lines isolated with 14 adults considered as extremes. iPSC lines have been established from 8 extremes, 4 with early onset dementia and 4 with late/no diagnosis of dementia. We have also reproduced some of the cellular phenotypes on primary human fetal neurospheres of T21 and gestational age matched normal controls, sampled in the Singaporean population.

Biography:

Xiushan Wu has obtained his PhD in Genetics from Stockholm University in 1990 and Postdoctoral studies in Developmental Biology at Michigan University during 1990-1994. He did his research as a Scientist in Molecular Genetics at Karolinska Institute in 1994-2000. He is a Professor and Director of The Center for Heart Development, Deputy Director of the Key Laboratory of the Ministry of Education of China for Developmental Biology and Protein Chemistry at Hunan Normal University, China. His research focuses on understanding the mechanisms by which embryonic heart is developed using Drosophila, zebrafish and mice as models. He has published more than 300 papers including over 100 papers in international journals.

Abstract:

The arguments regarding the origin of the endocardial progenitors remain unresolved. Here, we have identified a gene, tentatively named HPRG1 (heart progenitor regulation gene 1), through a large-scale screen of Drosophila mutants. The gene is expressed in heart valves in zebrafish and its expression pattern is conserved in mice. Knockdown of the gene resulted in a valve defect, suggesting it is involved in endocardial valve development. It is known that Isl1 or GATA4 positive cells are capable of differentiating into two cell types, endocardial and cardial progenitors and NKx2.5 is the direct activator of endocardial master regulator Etv2. Our results indicated that HPRG1 is expressed in a novel type of mesodermal progenitor cells that are co-expressed with each master regulators and HPRG1 activates the expressions of GATA4 and NKx2.5 and inhibits the expression of Isl1. It is especially interesting that HPRG1 determines the fate of a single cell of the 128-cells at zebrafish blastula stage, suggesting that it is a fate-determining gene. Thus, the HPRG1 positive blastula cells provide an appropriate experimental system for exploring the specification mechanism of the endocardial progenitors. A mechanism for heart valve progenitor specification beginning with HPRG1 through GATA4, Isl1 and NKx2.5 is under investigation.

Biography:

Prabhu develops strategic alliances and implements national and international projects for the mission of advancing regenerative medicine and stem cell therapy. Prabhu’s personal experience with life changing cellular therapies and adult stem cell transplant ignited his passion to be involved with an innovative new area of medicine bringing together the industry leaders in regulatory, science, medicine, safety and ethics via an association model to yield the best possible patients outcome.

Abstract:

Stem cells are undifferentiated cells that are present in the embryonic, fetal and adult stages of life and give rise to differentiated cells that make up the building blocks of tissue and organs. Medical definition of infertility is failure to conceive after > 12 months of unprotected intercourse reported by 1 in 6 couples. The major characteristics of stem cells are self-renewable, plasticity and potency. Peripheral blood derived concentrate contain growth factors like fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β) due to which stem cells considered as potentially new therapeutic agents for the treatment of infertility. Commonly stem cells are of two types: embryonic stem cells and adult stem cells (Hematopoetic stem cells and Mesenchymal stem cells). Another type is induced pluripotent stem cell which is generated by reprogramming of somatic cells. During past few years a considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. Platelet rich plasma (PRP) has shown a great success in treating thin endometrium which is a cause of failed IVF in infertile women. PRP secrete growth factors and increase the thickness of endometrium and increase the quality of blood flow. Bone Marrow concentrate may have potential role in treating Asherman Syndrome, Poor Ovarian Reserve, Oligospermia and non-obstructive Azoospermia. 

Biography:

Noha Mohammed Afifi Amin has completed her MD from Kasr Al-Ainy School of Medicine, Cairo University. She is appointed as Professor of Histology and Cell Biology since 2013. She is a Fellow of "Diploma of Health Profession Education" (DHPE) with honors, (2011) on line, in collaboration with Maastricht University, the Netherlands. She has published more than 15 papers in reputed journals.

Abstract:

Myelo-suppression is the most common toxicity encountered in the oncology clinic today. This study was planned to investigate the possible protective and therapeutic role of the traditional Chinese Medicinal Herb; Astragalus membranaceus (AM), on chemotherapy-induced myelo-suppression. This study was carried out on thirty six adult male albino rats. They were divided into: Group-I Control received phosphate buffered saline (PBS) solution. Group-II were injected IP with cyclophosphamide (CY) for 3 days (IIa) and continued for one more week to receive AM orally (gIIb). Group-III received CY IP together with AM orally for 3 days. Group-IV received AM orally for one week (gIVa) and continued for extra three days receiving CY IP with AM orally (gIVb). Blood samples were analyzed for Total Leucocytic Count and Lymphocytic Count. Counting of CD34 positive cells in bone marrow was performed by flowcytometry. Bone marrow sections were subjected to H&E stain as well as immunohistochemical staining for anti- CD20 antibody. The mean area percentage of cellular bone marrow regions occupied by developing hematopoietic cells, mean area of fat cells and mean number of CD20 immunopositive B-lymphocytes in the bone marrow were measured by histomorphometric studies and statistically compared. AM proved to have a myelo-protective and myelo-therapeutic capacity, evidenced at both laboratory and morphological levels. The greatest myelo-potentiating effect of AM was achieved when supplied before and together with CY therapy.

Biography:

Guillermo Estivill Torrus has completed his PhD from University of Malaga, Spain and Postdoctoral studies from University of Edinburgh Medical School (UK). From 2002, he is the Leader of the research group CTS643 “Applied Neuropsychopharmacology for Neurological and Neuropsychiatric diseases”. He is also a Co-Principal Researcher of the research group "Nhttp://stemcell-regenerativemedicine.conferenceseries.com/euroimmunology-Multiple Sclerosis" in the IBIMA and Manager of the Image Unit (common support structures for research) in the same institution. More than 30 articles reflect his research concerning mostly the role of regulatory lipid molecules, mainly lysophosphatidic acid on the central nervous system.

Abstract:

Lysophosphatidic acid (LPA) is an endogenous lysophospholipid acting as mediator in many cell types through specific G-coupled protein receptors (LPA_1-6). LPA has been also demonstrated as mediator in the central nervous system, inducing biological effects on various stem cell types, including neural and mesenchymal. The recent findings on the potentials of mesenchymal stem cells for therapy of autoimmune diseases, such as multiple sclerosis led us to search how LPA₁-dependent signaling pathway could well mediate effects for mesenchymal therapy efficiency because of LPA₁ roles in both biological systems, neural and mesenchymal. Murine adipose tissue derived mesenchymal stem cells (AMSCs) were obtained, cultured under standard conditions and examined for LPA receptors expression. AMSCs were exposed to LPA receptors agonist vs. antagonists (Ki16425, VPC32183) in order to analyze their effects on proliferation and differentiation, demonstrating also specific changes in surface receptors. To analyze their in vivo effect, we used a murine model for multiple sclerosis, the experimental autoimmune encephalomyelitis (EAE) induction, using MOG_35-55 immunization with a relapsing-remitting course. AMSCs were previously treated with LPA₁-modulators and analyzed in vivo. Subsequently, AMSCs vs. treated AMSCs were labeled and tracked after administration in EAE mice at different points of the clinical course. Our results demonstrated the presence of LPA-dependent signaling pathway in AMSC, suggesting a regulatory role in their behavior and involving pharmacological modulation as well.

Biography:

Ping Zhou is currently pursuing his PhD from Peking University, China. He has published 5 papers in reputed journals.

Abstract:

Human pluripotent stem cells (hPSCs) possess great value in the aspect of cellular therapies due to its self-renewal and potential to differentiate into all somatic cell types. A few defined synthetic surfaces such as polymers and adhesive biological materials conjugated substrata were established for the self-renewal of hPSCs. However, none of them was effective in the generation of human induced pluripotent stem cells (hiPSCs) and long-term maintenance of multiple hPSCs, and most of them required complicated manufacturing processes. Polydopamine (PDA) has good biocompatiblity, is able to form a stable film on nearly all solid substrates surface, and can immobilize adhesive biomolecules. In our study, carboxymethyl chitosan was used as a linker to orthogonally and controllably attach adhensive peptide to PDA coated cell culture plates for the culture of hPSCs. This synthetic surface was demonstrated that, it not only support the reprogramming of human somatic cells into hiPSCs under defined conditions, but also sustain the growth of hiPSCs on diverse substrates. Moreover, the proliferation and pluripotency of hPSCs cultured on the surface were comparable to Matrigel for more than 20 passages. Besides, hPSCs were able to differentiate to cardiomyocytes and neural cells on the surface. This polydopamine-based synthetic surface represents a chemically defined surface extensively applicable both for fundamental research and cell therapies of Human pluripotent stem cells (hPSCs) possess great value in the aspect of cellular therapies due to its self-renewal and potential to differentiate into all somatic cell types. A few defined synthetic surfaces such as polymers and adhesive biological materials conjugated substrata were established for the self-renewal of hPSCs. However, none of them was effective in the generation of human induced pluripotent stem cells (hiPSCs) and long-term maintenance of multiple hPSCs, and most of them required complicated manufacturing processes. Polydopamine (PDA) has good biocompatiblity, is able to form a stable film on nearly all solid substrates surface, and can immobilize adhesive biomolecules. In our study, carboxymethyl chitosan was used as a linker to orthogonally and controllably attach adhensive peptide to PDA coated cell culture plates for the culture of hPSCs. This synthetic surface was demonstrated that, it not only support the reprogramming of human somatic cells into hiPSCs under defined conditions, but also sustain the growth of hiPSCs on diverse substrates. Moreover, the proliferation and pluripotency of hPSCs cultured on the surface were comparable to Matrigel for more than 20 passages. Besides, hPSCs were able to differentiate to cardiomyocytes and neural cells on the surface. This polydopamine-based synthetic surface represents a chemically defined surface extensively applicable both for fundamental research and cell therapies of hPSCs.

Biography

Biography:

Aditya Borakati is currently a Medical student at the Hull York Medical School. He has a first class intercalated Degree in Regenerative Medicine from King’s College London with research into novel maxillofacial prostheses. He has a strong interest in surgery and research and is on the Steering Committee for the National STARSurg Collaborative.

Abstract:

Osteoarthritis (OA) is a major global burden creating significant morbidity worldwide. Current curative therapies are expensive, challenging to access and have significant risks, making them infeasible and difficult in many cases. Mesenchymal stem cells (MSCs) can be applied to joints and may regenerate the cartilage damaged in OA, this therapy may be advantageous to existing treatments. We systematically reviewed clinical trials of MSCs for cartilage repair and provide an overview of the literature in this area here. MEDLINE, Embase, CENTRAL, clinicaltrials.gov and OpenGrey were searched for controlled trials and case series with >5 patents involving MSC therapy for cartilage repair. The controlled trials were meta-analyzed and the primary outcome measure was improvement in pain over the control group. A narrative synthesis was composed for the case series. A significant reduction in pain was found with the use of MSCs over controls: Standardized mean difference=-1.27 (95% confidence intervals -1.95 to -0.58). However, the data was extremely heterogeneous with I²=95%, this may be attributed to differing therapies, clinical indication for treatment and joints treated amongst others. Case series showed improvements in treated patients with a variety of differing treatments and by many outcomes. There were no severe adverse outcomes found across all studies that could be attributed to MSCs, implying their safety. We conclude that MSCs have significant potential for the treatment of OA; however, larger, more consistent trials are needed for conclusive analysis.

Biography:

Pierre-Edouard Dollet is a Young Researcher in the stem cell therapy field. He has performed his Master degree Internship at Promethera Biosciences to study the feasibility of using a bioreactor to culture the liver stem cells. Presently, he has been studying the engraftment process of the liver stem cells during infusion and trying to improve it in a PhD program at Université Catholique de Louvain of Bruxelles.

Abstract:

ADHLSC infusions are undergoing clinical trials. As many MSCs, they are both facing low engraftment levels. MSCs appear to use a mechanism of rolling and firm adhesion similar to leukocytes to engraft in organs. They mainly use the couple of integrins VLA-4 to bind VCAM-1 on the endothelium and transmigrate as they do not express the other molecules involved in the process. Unfortunately, ADHLSCs express VLA-4 to a slight degree. Here we investigated the benefit of using alternative methods to culture and harvest ADHLSCs in order to avoid trypsinization. ADHLSC were cultured on a thermosensitive polymer and/or harvested using a non-enzymatic dissociation solution (NEDS) and their adhesion properties were compared to that of control cells cultured on CellBind® and harvested by trypsinization. Interestingly, we observed in a shear stress adhesion test a 44% increase of in the adhesion to VCAM-1 after culture on thermosensitive polymer combined with harvesting with NEDS compared to the control condition (P<0.001). Similarly, adhesion to non-activated HUVEC was increased by 3.2 fold change after Polymer and NEDS compared to CB and Trypsin (P<0.001). However, no significant differences were found when the test was performed on TNFα-activated HUVECs. Together, these results suggest that the culture condition Polymer NEDS has a benefic effect on the adhesion of ADHLSCs to endothelial proteins, particularly under normal conditions where these proteins are expressed at a lower level. These culture conditions could be used clinically in stem cells therapy, to improve the engraftment of the cells especially in the context of non-inflammatory diseases.

Biography:

Anna Andrzejewska has completed her studies in Faculty of Biology at University of Warsaw at the age of 24. She obtained her master degree in biotechnology with specialization in molecular biology in 2012 and then started her PhD studies in Mossakowski Medical Research Centre Polish Academy of Sciences at NeuroRepair Department under supervision of Barbara Łukomska Professor of Immunology and Transplantology. She has already attended 5 conferences including 2 international conferences, where she presented short communication of her results. She has published one paper and currently 2 more publications are in preparation.

Abstract:

Introduction: Mesenchymal stem cells (MSCs) are of great interest in regenerative medicine. Their plasticity and low immunogenicity gains them credibility as therapeutic agents in tissue injured disorders. The success of clinical application of MSCs relies on their recruitment into damaged tissues. Systemic infusion of MSCs is minimally invasive method however cell migration into desired organs is inefficient. We hypothesize that induction of integrin overexpression in MSCs will enhance their adhesion and migration through the endothelial wall.

Aim: The goal of our study was to induce the expression of ITGA-4 (VLA-4 subunit) via mRNA based method and to test whether this overexpression leads to increased adhesion of human bone marrow derived MSCs (hBM-MSCs).

Methods: The naive and mRNA-ITGA4 transfected hBM-MSCs (Lonza) labeled with iron nanoparticles and Rhodamine-B was used. The microfluidic and transwell assays with surfaces coated with VCAM-1 were employed to estimate functionality of modified MSCs in vitro.

Results: In microfluidic assay MSCs were observed to roll, capture and arrest into microchannels. Quantitative analysis showed that the average flow speed of VLA-4 over-expressing MSCs was smaller (27.5 pixels/frame) than the flow of naive cells (76 pixels per frame). Also, the percentage of arrested MSCs was higher in case of modified cells than of control MSCs (14% vs. 2.8%). Similarly, in transwell assay we observed reduced migration of transfected MSCs compared to non-transfected cells.

Conclusions: Our in vitro studies have shown superior adhesive properties of mRNA-ITGA-4 engineered hBM-MSCs over their naive counterparts. Modification of adhesive proteins on MSCs surface seems to be interesting perspective in their clinical settings.

Biography:

Raili Koivuniemi has completed her PhD from Faculty of Biosciences, University of Helsinki in 2013. Presently, she works as a Postdoctoral researcher at Division of Pharmaceutical Biosciences, University of Helsinki, Finland.

Abstract:

Stem cell transplantation has shown promise to promote wound healing. In the wound, stem cells could regulate inflammation and secrete supportive growth factors and thus, endorse tissue homeostasis and regeneration of the injured tissue. However, transplanted stem cells usually show limited survival due to the hostile environment in injured tissue. In addition, transplanted stem cells may be lost due to compromised attachment and spreading. Therefore, stem cell survival and retention are subjects to be improved towards successful cell therapy. The aim of this project is to study interactions between human adipose stem cells (hASCs) and a novel wood derived nanofibrillar cellulose (NFC) materials and signaling pathways involved in stimulation of hASCs, in order to develop cell transplantation methods for wound care. Adipose stem cells are multipotent cells from mesenchymal origin that are easily available from subcutaneous adipose tissue by a lipoaspiration procedure. During the project, hASC characteristics will be evaluated when cultured on NFC membrane or embedded into NFC hydrogel. Results show that culturing of hASCs on NFC membrane maintains cell characteristics and survival. The use of mechanical strength during the delivery may enhance cell retention. Thus, hASC culturing on NFC membrane that could be used as a dressing material for wound treatment may serve as an efficient delivery method into the wound. On the other hand, culturing of stem cells in three-dimensional environment could improve cell retention and survival. Moreover, the knowledge of signaling pathways that stimulate hASCs is of importance for preconditioning of cells prior to transplantation.

Biography:

Yung-Feng Liao has completed his PhD from University of Georgia, Athens, GA, USA in 1998 and Postdoctoral studies from Harvard Medical School and affiliated hospitals. He is an Associate Research Fellow of Academia Sinica, a premier research institution in Taiwan. He has published 47 peer-reviewed papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common form of dementia in the elderly. The lack of disease-modifying therapeutics for AD has imposed a huge social burden. Accumulated evidence has suggested that neurotoxicity elicited by of amyloid-β (Aβ) and Tau, the two pathological hallmarks of AD, significantly contribute to the pathogenesis and progression of AD. It has been proposed that neurogenic agents with neuroprotective efficacy could be potential therapeutics for AD by reviving the neurogenesis of endogenous neural stem cells to replace the lost neurons in the diseased brain. We thus seek to identify novel neurogenesis-promoting agents from herbal extracts and determine whether herbal extracts effective on inducing neurogenesis can reduce Aβ-elicited neurotoxicity. An in vivo neurogenesis assay is established to perform the primary screen of herbal extracts. Effective herbal extracts are validated by a secondary zebrafish model of tauopathy independently. The in vivo efficacy of herbal extract is subsequently determined by using an Aβ42-injection mouse model of AD. We have now identified an herbal extract (HE238) that exhibit biological efficacy in promoting in vivo neurogenesis and concomitantly suppressing the neurotoxicity elicited by amyloidopathy. Our data show that treatments with HE238 can effectively induce neurite outgrowth and promote the clearance of Aβ and Tau. Oral administration of HE238 for 2 month also significantly improves the cognitive function in an Aβ42-injection mouse model. Together, our data suggest that the active ingredients of HE238 could present an enormous resource for AD-alleviating agents.

Biography:

Bahareh Ghasemi has completed her study in Medicine from Medical School of Arak Medical Science University in Iran in 2004 and she is currently a PhD student.

Abstract:

Mesenchymal stem cells (MSCs) are adult stem cells with the capacity for self-renewal and differentiation into osteoblast, adipocyte and chondrocyte lineages. MicroRNAs (miRs) are a class of small non-coding RNAs of 20-22 nucleotides molecules which suppress protein synthesis and regulate many aspects of cell function. Therefore the aim of this study was to investigate the hypothesis that miRNAs may regulate cell fate of MSCs. MSCs were tested for differentiation into osteoblast, chondrocyte and adipocyte lineages by qRT-PCR for lineage specific genes. To identify miRNAs involved in MSC differentiation we used a miRNA PCR-array. 5 miRNA were selected based on their significant up/down-regulation in array, as unknown miRNAs in MSC differentiation, according to previous studies, for further investigation. Next, their expression was validated by qRT-PCR. Finally, to determine the role of the miR-302 family during MSC differentiation, their functional activity was tested by knockdown using miRNA inhibitors. MSCs showed osteoblast, chondrocyte and adipocyte differentiation on induction with specific culture media. In the PCR array members of the miR-302 family were down regulated and this was confirmed during MSC differentiation, by qRT-PCR. Knockdown of miR-302 resulted in an 80% and 50% decrease in miR-302 band an expression respectively. Transfection of MSCs with miRNA inhibitor resulted in increase in osteocalcin (BGP) and ALP expression during osteogenesis and in FAB, PPARg and CEBP during adipogenesis. The results suggest that miR-302 may be an inhibitor of osteogenic and adipogenic differentiation of MSCs and may maintain stem cell properties. Further investigations are in progress on the effect of miR-302 overexpression.

Biography:

Monica Maribel Mata Miranda is a Professor and Laboratory Head of Cell Biology at Escuela Medico Militar, Mexico. She has earned her BSc in Medicine at Escuela Medico Militar and MD with honor in Biomedical Sciences from Escuela Militar de Graduados de Sanidad. Presently, she is a PhD candidate at Centro de Investigación en Biotecnología Aplicada of the Instituto Politecnico Nacional. Her work is based on stem cells applications and differentiation.

Abstract:

Anal sphincter disruption is one of the most common causes of fecal incontinence as a result of obstetric anal sphincter injury, anorectal surgery or trauma, with few therapeutic options. Stem cells therapy has shown the benefits for tissue restoration and immunomodulation. Therefore, the aim of this study was to analyze the histological and functional effects after implanting mouse Pluripotent Stem Cells (mPSCs) in a murine model with anal canal injury (ACI). To develop this research, 42 female Wistar rats were subjected to ACI and divided into 3 groups. Group 1 (control group) was treated with 300 μl of isotonic saline solution (ISS), group 2 (late treatment, 30, 37 and 45 days after ACI) and group 3 (early treatment, 24 hours, 7 and 14 days after ACI) received 50,000 mPSCs resuspended on 300 μl of ISS. All animals were evaluated by high resolution manometry 24 hours before and after ACI and 3 months after ACI. Finally, rats were sacrificed on the third month and histopathological sections from anal canal were obtained. Physiological results showed that the groups treated with mPSCs presented higher basal electrical activity and maximum voluntary squeeze pressure measures 3 months after ACI, highlighting the statistical significance on group 3. Moreover, histopathological results evidenced better restoration of the histological architecture on experimental groups showing neoformation of fibroblasts and capillaries. In conclusion, PSCs implant on ACI improve anal sphincter tone as well as histological architecture, presenting better regenerative results when they are implanted as an early treatment.

Biography:

Shicheng Wei has completed his PhD from West China University of Medical Sciences. He has published more than 60 papers in reputed journals relating to fields of biomedical materials and tissue engineering, basic and clinical research of stomatology.

Abstract:

Hyaluronic acid (HA) has been cross-linked to form hydrogel for potential applications in the self-renewal and differentiation of human pluripotent stem cells (hPSCs) for years. However, HA hydrogel with improved residence time and mechanical integrity that allows the survival of hPSCs under defined conditions is still much needed for clinical applications. In this study, HA was modified with methacrylate functional groups (MeHA) and cross-linked by photo cross linking method. After subsequent conjugation with adhesive peptide, these MeHA surfaces demonstrated performance in facilitating human induced pluripotent stem cells (hiPSCs) proliferation, and good pluripotency maintenance of hiPSCs under defined conditions. Moreover, MeHA films on glass-slides exhibited long residence time and mechanical stability throughout hiPSC culture. Our photo-cross linkable MeHA possesses great value in accelerating theapplication of HA hydrogel in hiPSCs proliferation and differentiation with the conjugation of adhesive peptides.

Biography:

Gustavo Jesus Vazquez Zapien is a Professor and Laboratory Head of Embryology at Escuela Medico Militar, Mexico. He has earned his BSc in Medicine at Escuela Medico Militar and MD with honors in Biomedical Sciences from Escuela Militar de Graduados de Sanidad. Presently, he is a PhD candidate at Centro de Investigación en Biotecnología Aplicada of the Instituto Politecnico Nacional. His work is based on stem cell applications and differentiation.

Abstract:

An essential property of stem cells (SCs) is the potentiality, which refers to their capability to differentiate into different cell lineages under certain culture conditions. Two of the greatest challenges in SCs biology and regenerative medicine are differentiation control of SCs and to ensure the purity of differentiated cells. In this work, mouse Pluripotent Stem Cells (mPSCs) were subjected to a differentiation protocol of 21 days obtaining Differentiated Pancreatic Cells (DPCs), characterizing this differentiation process by spectroscopic and genetic analysis through Fourier Transform Infrared (FTIR) spectroscopy and Real-Time PCR. FTIR spectra of mPSCs and DPCs at different maturation stages (11, 17 and 21 days) were obtained and showed absorption bands related with different types of biomolecules. These FTIR spectra exhibited significant changes particularly in the proteins, carbohydrates and nucleic acids bands agreeing with the differentiation process. The second derivative of these bands and the Principal Components Analysis allowed us to compare and discriminate mPSCs from DPCs. About gene expression, mPSCs expressed pluripotency genes (Nanog and SOX2) and the DPCs expressed endodermal genes (SOX17 and Pdx1) at day 11, an inductor gene of embryonic pancreas development (Pdx1) at day 17 and pancreas genes (Insulin and Glucagon) at day 21 of differentiation. In conclusion, we obtained DPCs from mPSCs, which passed through the chronological stages of embryonic pancreas development. The FTIR spectral changes provide a new biophysical parameter based on molecular markers that indicate the differentiation process of mPSCs to specialized cells.

Biography:

Malgorzata Majchrzak, M. Sc. graduated from University of Medical Sciences in Poznan. In 2015, she joined the Mossakowski Medical Research Centre at Polish Academy of Sciences to seek a PhD degree in the field of neurobiology. Her PhD project in NeuroRepair Department of MMRC is concentrated on therapeutic potential of glial restricted progenitors in amyotrophic lateral sclerosis (ALS) treatment. She takes part in two international research projects funded by National Center for Research and Development in Poland: “Application of Glial Progenitors for Treatment of ALS” and “MRI-guided, intrathecal delivery of hydrogel-embedded glial progenitors for treatment of amyotrophic lateral sclerosis”.

Abstract:

Introduction: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with no available treatment that leads to death in less than five years after diagnosis. The experimental studies show a great potential of glial restricted progenitors (GRPs) in treatment of many neurodegenerative disorders, including ALS. One of the greatest advantages of GRPs is their ability to differentiate into both oligodendrocytic and astrocytic cell lineages that play a key role in supporting axon homeostasis and protection of motor neurons. Moreover, mature glial cells are also responsible for myelination processes.

Material & Methods: GRPs were extracted from brain and spinal cord of embryonic (E15) transgenic GFP mice (mGRPs) and (E30-35) dogs (dGRPs). Isolated cells were cultured in GRP designed medium (DMEM/F12+B27+N2+heparin+BSA+bFGF) in flasks coated Poly-L-lysine and laminin. GRPs were selected by medium composition and cultured up to the second passage. Both types of GRPs were characterized by immunocytochemistry analysis using the specific primary antibodies: A2B5, GFAP, PDGFRα, MBP, O4, Ng2, CNPase, Olig1, Olig2, Ki67 and CXCR4.

Results: Both type of cells, mGRPs and dGRPs show positive reaction with antibodies against early markers of glial progenitors (GFAP, Olig2, CNPase) and negative for mature oligodendrocytes (MBP). They reveal positive markers for proliferation (Ki67) and migration (CXCR4) abilities.

Conclusion: The current study shows that cells isolated from fetal nervous system, both mouse and canine have high ability to differentiate into glial progenitor cells. In the future studies, both lines will be used in vivo to assess their therapeutic potential in different experimental ALS mouse models.

Biography:

Barbora Hermankova is currently a PhD student in the field of Immunology at the Faculty of Science, Charles University in Prague. She prepared her dissertation thesis at Department of Transplantation Immunology at Institute of Experimental Medicine, Academy of Sciences of the Czech Republic. Her work is focused on the study of mesenchymal stem cells (MSC) and their immunomodulatory effects. MSC are able to suppress immune response and she studies mechanisms of this suppression which can be mediated by a cell contact, production of soluble factors or by other ways.

Abstract:

Mesenchymal stem cells (MSCs) are a good candidate for regenerative medicine and treatment of various diseases. They are able to suppress immune response by a cell contact, production of soluble factors and by other mechanisms. In this study we analyzed the effects of mouse bone marrow-derived MSCs on IL-10 production by lipopolysaccharide (LPS) activated B cells. The production of IL‑10 by B cells was significantly enhanced in the presence of IFN-γ. Untreated MSCs had no significant effect on IL-10 production by B cells. However, when B cells were co-cultured with MSCs and IFN-γ, the production of IL-10 was strongly suppressed. Moreover, a similar effect was observed when MSCs were pre-incubated with IFN-γ and then co-cultured with activated B cells. On the other hand, the production of IL‑10 was unchanged after cultivation IFN-γ pre-treated B cells with MSCs. A strong up-regulation of genes for indoleamine‑2,3‑dioxygenase (IDO), cyclooxygenase 2 (COX-2) and programmed cell death ligand-1 (PD-L1) was detected in MSCs treated with IFN‑γ. To identify the molecule which is responsible for the suppression of IL-10 production, we used neutralization monoclonal antibody anti‑PD‑L1 or inhibitors of IDO and COX-2. The suppression of IL-10 production was abrogated only in cultures with inhibitor of COX-2. The suppressor effect of COX-2 involving pathway was verified by adding prostaglandin E2 (PGE2) to the cultures with activated B cells. The mechanism of MSC mediated inhibition of IL-10 production by LPS-activated B cells requires a direct contact between B cells and MSCs and involves COX-2 pathway leading to the production of inhibitory PGE2.

Biography:

Michaela Hajkova is currently a PhD candidate at Charles University in Prague, Faculty of Science. She has completed her Master’s degree in Biology with thesis entitled “The role of selected cell populations and molecules in inflammatory reaction and rejection of skin allograft”. She is working in the Laboratory of Immunoregulation where she is participating in research of therapeutic potential of MSCs and their ability to contribute to tissue repair.

Abstract:

The immunosuppressive effects of systemically administered mesenchymal stem cells (MSCs) and immunosuppressive drugs have been well documented. In several studies it has been shown that the administration of MSCs in combination with different types of immunosuppressive drugs prolongs allograft survival for a longer period of time than the use of MSCs or the drug alone. In our study mechanism of therapeutic effect of MSCs applied locally in combination with cyclosporine A (CsA) in a mouse model of allogeneic skin transplantation was analyzed. We have shown that MSCs seeded on a CsA loaded nanofiber scaffolds applied on skin grafts migrated to the graft bed and draining lymph nodes and altered individual parameters of the local immune response. Among the most significant effects decreasing amount of graft-infiltrating macrophages and their production of nitric oxide was detected. These changes were accompanied with considerable lower production of interferon-gamma cytokine that primes classically activated macrophages. Switch from the proinflammatory, NO producing, M1 phenotype into alternatively activated M2 population of macrophages was further confirmed by the up-regulation of CD206, a marker of M2 population and by significant increase of production of IL-10 by CD206 positive macrophages. In this study we found that application of MSCs in combination with CsA direct macrophage polarization towards development of “healing” alternatively activated macrophage population that might represent important mechanism of MSC-induced suppression of the local inflammatory reaction.

Biography:

Mohamed Gamal El-Beltagy is currently a Graduate student at Faculty of Dentistry, Mansoura University, Egypt. He works as a Research Assistant in Mansoura Medical Research Center (MERC) in Faculty of Medicine, Mansoura University and he is a Director on a project entitled “Dental Pulp Stem Cell Banking” funded by the Ministry of Higher Education in Egypt under supervision of Professor Mohamed Sobh.

Abstract:

Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells (MSCs) and represent a suitable alternative source of it. DPSCs are multipotent stem cells that have the potential to differentiate into a variety of cell types for the purpose of cell-based therapies. Isolation and banking of DPSCs has attracted a large number of researchers who are interested in the area of stem cell as it is relatively easy to obtain using low invasive procedures, as it is easily obtained from the teeth extracted for orthodontic treatments, impacted 3^rd molar teeth or normal shedding process of Childs. Pulp is located in one of the strongest structures in the living body; this makes it a challenge to isolate this tissue completely. In this study we introduce a new innovating way to obtain the pulp tissue completely without heat generation that affects the pulp and cause its distortion. It is a comparative study between the two types of digestion: Enzymatic and Direct outgrowth explants technique, comparative study between the different interval of time from extraction of teeth to isolation time to determine the optimal time recommended for isolation of DPSCs and also comparing between isolation of pulp immediately after extraction and after specific intervals of time. We also studied possibility of isolation from dentine carious tooth or even tooth surrounded by lesions. By using the 4 characteristic genes of DPSCs: MSX1, MSX2, TBX2, ENTPD1, we compare their degree of expression in different passages. Finally, DPSCs isolation is done using flow cytometery cell sorting by antigens surface markers CD90, 73, 105 positive markers and CD34, 45, 14 negative.

Biography:

Naglaa Kamal Idriss has completed her PhD from Birmongham University funded by the Egyptian Cultural and Educational Bureau/Center in London and Postdoctoral studies from Southampton University, UK. She is the Member of ISSCR, ESC and Acute Cardiac Care Association. She has published more than 15 papers in reputed journals.

Abstract:

Biography:

Eliska Javorkova completed her PhD study at Charles University in Prague with thesis “The use of immunoregulatory properties of mesenchymal stem cells and their therapeutic potential” in 2014. She has published 15 papers in journals with IF, total IF of her publications is 58,679. Her research project is focused on migratory and immunomodulatory properties of mouse and human mesenchymal stem cells.

Abstract:

In this study we investigated the effects of systemically administered bone marrow-derived mesenchymal stem cells (MSCs) on the early acute phase of inflammation in the damaged eye. The surface of eye was damaged by the application of filter paper soaked with 1 M NaOH for 30 seconds. MSCs were prepared from a population of bone marrow cells of BALB/c mice and were depleted of CD11b⁺ and CD45⁺ cells using a magnetic activated cell sorter. Mice with damaged eye were either untreated or treated 24 hours after the injury with an intravenous administration of fluorescent dye-labeled MSCs that were unstimulated or pretreated with interleukin-1α (IL-1α), transforming growth factor-β, or interferon-γ (IFN-γ). Analysis of cell suspensions prepared from the eyes of treated mice on day 3 after the alkali burn revealed that MSCs specifically migrated to the damaged eye and that the number of labeled MSCs was more than 30-times higher in damaged eyes compared with control eyes. The study of the composition of the leukocyte populations within the damaged eyes showed that only MSCs pretreated with IFN-γ significantly decreased the percentage of eye-infiltrating cells. The analysis of cytokine and NO production in the damaged eyes showed that the most effective immunomodulation was achieved with MSCs pretreated with IFN-γ, which significantly decreased the levels of the proinflammatory molecules IL-1α, IL-6, and NO. The results show that intravenously administered MSCs specifically migrate to the damaged eye and that IFN-γ-pretreated MSCs are the most effective in inhibiting the acute phase of eye inflammation.

Biography:

Sadegh Golie has completed his Master’s degree from Iran Polymer and Petrochemical Institute. He had a Polymer Material’s background in the Bachelor degree and has changed it to the Biomaterial Interdisciplinary field. He has focused on the corneal tissue engineering by using the bioplymers and novel fabrication methods and he is also currently studying renaturation of the gelatin to collagen.

Abstract:

Electrospinning of gelatin aqueous solutions has been the ultimate goal of enormous studies over the last decade because of bio-related advantages of using water. In order to achieve optimal gelatin nanofibers in aqueous systems, both the syringe and the chamber temperatures, which have not been investigated thoroughly in the related literature, must be considered as they determine whether electrospinning process is accessible. In this study, we designed and utilized two thermal devices (a chamber heater and a syringe dressing heater) to simultaneously achieve perfect morphology and efficient production rate. In spite of our endeavors to optimize process of spinning by heating, an efficient, steady process could not be obtained due to immediate occurrence of material gelation. By and large, exceeding over 50 °C inspired the assumption that the high viscosity is not the sole reason to disrupt the process. To prove it, we present two hypotheses based on effects of solution viscosity and surface tension on the process. Rheological investigation revealed that initial gelation temperature plummeted about 2 °C while pH was increased 6.5 units. Also, control on ion content of the solution was necessary to investigate the role of surface tension (monitored by contact angle measurements) in gelation. In conclusion, although viscosity should be controlled by heating procedures, window of efficient spinning was opened by proper surface tension adjustment of solution, which permits molecules to jet and prevents clogging at nozzle. This approach leads to a continuous and perfect process of spinning and formation of 3D scaffolds for biomedical purposes.