Helen McGettrick has completed her PhD in 2006, followed by three Post-doctoral research positions at the University of Birmingham (UK). She was appointed as a University Fellow in Inflammation Biology in 2011, and a year later successfully won a five year Arthritis Research UK Career Development Fellowship. She was recently awarded the prestigious Garrod Prize by the British Society for Rheumatology in 2016. She is currently a Senior Research Fellow at the University of Birmingham and an Honorary Lecturer at the University of Glasgow and Newcastle University (UK). She has ~40 published articles with ≈ 760 citations, has filed three patents and received funding from Wellcome Trust, Medical Research Council UK, Pfizer and British Heart Foundation.

Mesenchymal stem cells (MSC) are tissue resident stromal cells with immunomodulatory properties which are increasing used therapeutically via injection into the blood. Within the blood and tissue, their adhesive and migration properties, along with their interactions with other blood cells may influence their fate. Human bone marrow (BM) or umbilical cord (UC) MSC adhered from flow to matrix proteins. However, they displayed distinct interactions with platelets when perfused in whole blood, with only UCMSC inducing platelet aggregation and causing a marked drop in platelet count when infused systematically into mice. UCMSC, but not BMMSC, expressed a mucin-like protein called podoplanin, which is known to bind to CLEC-2 expressed on platelets. Expression of podoplanin varied in UCMSC donors; most were positive, but some donors lacked expression (podoplanin negative). Only podoplanin-positive UCMSC were able to aggregate platelets in vitro and in vivo, and this could be blocked by competitive inhibition with recombinant CLEC-2. Human UCMSC caused reduction of platelet count when mixed with mouse blood, but the response was lost with blood taken from mice deficient in CLEC-2. Separately we observed that podoplanin expression enhanced UCMSC migration in vitro in a Rac-1 dependent manner. Thus, the origins of MSC and their expression of podoplanin may have impact on their behavior in blood and tissue. During therapy, MSC interactions with platelets could be thrombotic, but might also promote targeting of MSC to damaged tissue, where they could exert their reparative and immunomodulatory effects.

G Ian Gallicano has completed his PhD in 1994 from Arizona State University afterwhich he has completed his Post-doctoral studies at The University of Chicago/Howard Hughes Institute. He has been the Director of the Transgenic Shared Resource at the Lombardi Comprehensive Cancer Center and is currently implementing CRISPR gene editing technology at GUMC. He has published more than 60 papers in reputed journals and is currently an Editorial Board Member for the journal Stem Cells as well as the Editor-in-Chief for American Journal of Stem Cells.

MicroRNAs are quickly entering the causal fray of developmental defects. These small, non-coding RNAs use a 7-8 basepair seed sequence to target a corresponding sequence on one or multiple mRNAs resulting in rapid down-regulation of translation. miRNAs can also control protein amounts in cells. As a result, if miRNAs are over or under expressed during development protein homeostasis can be compromised resulting in defects in the development of organ systems. Here, we show that during differentiation of embryonic stem cells, individual miRNAs that reside in the miRNA17 family (composed of 15 miRNAs) do not share the same function even though they have the same seed sequence. The advent of CRISPR/CAS9 technology has not only yielded a true observation of individual miRNA function, it has also reconnected advanced molecular biology approaches to classical cell biology approaches such as gene rescue. We show that miRNA106a and to a lesser extent miR17 and 93 target the cardiac suppressor gene Fog2, which specifically suppress Gata-4 and Coup-TF2. However, when each miRNA is knocked out, we find that their targeting efficacies for Fog2 differ resulting in varying degrees of cardiac differentiation.

Adalberto L Rosa, DDS, MSc, PhD, is working as a full Professor of Oral and Maxillofacial Surgery in the University of São Paulo, Brazil. He has been developing research projects focused on Tissue Engineering and Cell Therapy aiming at bone repair using either in vitro or in vivo models.

Cell therapy has been investigated as a promising treatment for bone defects in situations where the trauma extension surpasses the bone regenerative capacity. In this scenario, the aim of our study was to evaluate the effect of mesenchymal stem cells (MSCs) and osteoblasts (OBs) on bone repair. Bone marrow MSCs were harvested from rat femurs, selected by adherence to polystyrene and characterized by the expression of a panel of surface markers. OBs were differentiated from these MSCs by culturing them in osteogenic medium and characterized by the gene expression of bone markers. Defects with 5-mm diameter were created in rat calvarias and after 2 weeks they received a direct injection of: (1) MSCs, (2) OBs (5*106 cells in 50 μL of PBS for each cell type) or (3) PBS without cells (control). Bone formation was evaluated 4 weeks post-injection by microtomographic and morphometric analyses. The data were compared by ANOVA (n=12, p≤30.05). MSCs presented a high percentage of cells expressing CD29 and CD90 and a low percentage expressing CD31, CD34, CD44 and CD45. OBs displayed higher gene expression of ALP, OC and OPN. Luciferase-expressing MSCs and OBs were detected within the defects till 12 days post-injections. The 3-D microtomography reconstructions as well as morphometric parameters showed more bone formation in defects injected with cells compared with control. Bone volume (p=0.03), % bone volume (p=0.03) and trabecular number (p=0.05) were higher in cell-injected defects, trabecular separation (p=0.002) was lower while bone surface (p=0.07) and trabecular thickness (p=0.4) were not affected by treatments. There was no difference between MSCs and OBs-injected defects in any of the evaluated parameters. The results show that the treatment of calvarial defects with cells irrespective of the differentiation stage increased bone repair suggesting that cell therapy is a potential strategy to induce bone regeneration in challenging clinical conditions.

Sean Berman has completed his BS at Amherst College and his MS at Louisiana Tech University. As a college quarterback, he saw first hand effects of traumatic brain injury and realized the clear lack of active treatment options avaiable. He has been researching brain injuries and stem cells in the laboratory setting for 5

years now and actively collaborates with physicians in the hopes of developing clinically relavent reserach, findings and solutions.

Traumatic brian injury results after a blow to the head induces a terminal change in velocity causing the brain to be displaced beyond the blood brain barrier. This impact causes a cascade of cellular injuries. The initial injury is vascular and effects neuronal cells as well. The secondary injury is autoimmune in nature. Adipose derived mesenchymal stem cells (ADSCs) have the ability to migrate to sites of injury (inflammation) and repair damaged neuro-vascular tissue. They also can mitigate immune responses due to their immuno-modulatory characteristics. The first part of our study examined the use of fresh stromal vascular fraction (SVF), which contians ADSCs and hematopoetic stem cells (HSCs), delivered via tail vein injection, to mitigate the effects of shockwave induced TBI. The administration of SVF imporved both memory and motor skills functions. Another model was developed to model chronic traumatic encephalopathy (CTE) in the rat model. In this follow up study, rats received a shockwave induced TBI once a week for 10 weeks, followed by 1 million culture expanded ADSCs via tail vein injection (saline control). The rats were monitored for memory and motor skills. Histology was performed and showed human nucleated cells homed in on the site of injury and developed into functional tissue. These two studies show that cell treatmnet improves patient with acute brain injury and can prevent otehrwise long term expected side-effects of CTE.

MinYoung Kim is currently working as Professor and Director of Department of Rehabilitation Medicine and Rehabilitation and Regeneration Research Center,

CHA University, Korea. She graduated from Yonsei University College of Medicine, Seoul, Korea in 1991. She obtained her Doctor of Medical Science degree in 2002 and worked as a Post-doc for UCSanDiego in 2007-2008. She has been served as a Senior Editor of American Journal of Stem Cell, and Associate Editor of Restorative Neurology and Neuroscience. She published more than 34 articles of SCI and PubMed journals during past 7 years. Her fields of research interest are "application of stem cells for brain disease" and "brain rehabilitation".

Umbilical cord blood (UCB) cells have been suggested to exert therapeutic effect for cerebral palsy (CP). By conducting double-blind randomized controlled trials, we could observe the safety and efficacy of allogeneic UCB infusion in CP subjects. Physical and mental function evaluations using standardized measures including Gross Motor Performance Measure, Gross Motor Function Measure, and Bayley Scales of Infant Development-II Mental and Motor scales, and muscle strengths of extremities, showed therapeutic efficacy of UCB cells. To assess therapeutic mechanism of UCB in CP, 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) and diffusion tensor images were also used. 18F-FDG-PET/CT showed activation of basal ganglia and thalami and anti-inflammatory findings in periventricular white matter after UCB administration. Diffusion tensor images suggested improvement in white matter integrity which correlated with motor performance. According to molecular works using blood samples of the CP subjects, we found possible role of innate immune response triggered by UCB infusion. Elevations of pentraxin 3 and interleukin-8 levels in plasma and toll-like receptor 4 expression in blood cells were observed up to 12 days after UCB treatment and those correlated with the motor improvements observed up to 6-month post-injection.

As people are living longer, they are more likely to acquire chronic diseases or develop age-related conditions. Globally, there is an increasing incidence of chronic and degenerative diseases. In Helsinki Declaration, the innovative therapy has a sacred place in the advancement of medicine, and the role of the scientist diffusing the good information has been blessed since days of Hippocrates. Since the first decade of the 21st century, a widespread group of stem cell scientists lead a marvelous innovation in medicine, but also a tough confrontation with some sides. We aim to show the good of this new sector and that our work has its transparent purpose; to accelerate the process of knowledge about regeneration. Looking for a more satisfying solution at all medical levels, we developed at ACE Cells Lab the Regentime® procedure which is based on the transplantation of proliferated partially differentiated and specifically redirected autologous adult bone marrow derived mononuclear progenitor stem cells. After 9 years of devotion for regenerative medicine based on technique development, academic lecturing, and conferencing, we tend today to emphasize the importance of stem cells as a biological noble tool in our war against diseases.This presentation is reviewing, discussing, and analyzing the latest in stem cells field, all into a homogenous corpus serving the new generation of medics, enlightening the way for a better health. At the end, we will expose results of different research therapies in a realistic figure facilitating to physicians the act of choosing the best stem cell therapeutic methods, making the expected result clearer.

Nadja Zeltner has received her PhD from Ichan School of Medicine at Mount Sinai in New York and has completed her Post-doctoral studies from Dr. Lorenz

Studer’s laboratory at Memorial Sloan Kettering Cancer Center in New York. Her research focuses on disease modeling using human pluripotent stem cells with particular focus on the peripheral nervous system (PNS). Her ultimate goal is employing this technology to further understand PNS disorders that will lead to the development of novel drugs and therapeutics. She has started her own research group at the Center of Molecular Medicine at the University of Georgia

Functional and molecular aspects of human genetic disease can be recapitulated in vitro using patient-specific pluripotent stem cells (PSCs). Familial Dysautonomia (FD) is a debilitating developmental and degenerative disorder that primarily affects derivatives of the neural crest (NC), such as the peripheral nervous system (PNS). For unknown reasons, FD patients present with mild or severe disease despite carrying the identical, homozygous point mutation in IKBKAP. We present in vitro phenotypes at various stages of development that capture severe and mild FD in human PSC-derived cellular lineages. Patient-specific cells only from severe but not mild FD display an impaired capacity of developing into NC derivatives, such as autonomic and sensory neurons, thus they have neurodevelopmental defects. Interestingly, however, both severe and mild FD cells show defects in peripheral neuron survival, indicating neurodegeneration as the primary culprit in mild FD. Importantly, we found that neuronal degeneration in mild FD can be halted by treatment with candidate therapeutic compounds kinetin and SKF-86466. Genetic rescue of the FD mutation in severe FD iPSCs reversed NC, but not sensory neuron lineage phenotypes, implicating that the known FD mutation does not account for all symptoms. Employing whole-exome sequencing (WES), we identified candidate mutations that were only found in severe but not mild FD patients, providing evidence that FD may constitute two genetic sub-diseases. Our study demonstrates that human PSC-based disease modeling is sensitive in recapitulating disease severity and paves the road for applications in personalized medicine. Using a chemical screen, we identified a compound that could rescue severe FD defects. This further paves the way towards future treatments tailored more specifically towards individual patients.

Diana Anderson has completed her PhD from the University of Manchester, UK in the Faculty of Medicine. She is the Established Chair in Biomedical Sciences at the University of Bradford. She has published more than 450 papers and 9 books, successfuly supervised 32 PhD studnets, has an Hirsch factor of 55. She is Editor-in-Chief of a Book series for the Royal Society of Chemistry and is a Consultant to many internaitional organisations, such as the World Health Organisation/International Programme of Chemical Safety. She is/has been Member of the Editorial Board of 10 international journals.

Exposure to silver nanoparticles (AgNPs) has been reported to be related to male reproductive toxicity in mammalian studies. The present study explored the mechanism of cytotoxic and genotoxic effects of AgNPs on a primary culture of mouse Sertoli cells in vitro. DNA damage was evaluated in the Comet assay; apoptotic cells were detected using terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labelling (TUNEL) assay and apoptosis markers such as p53 and bcl-2 and antioxidant enzymes such as catalase (CAT), glutathione peroxidase 1 (GPX-1) and superoxide dismutase 1 (SOD-1) were quantified using qPCR. The superoxide anion was detected using the nitroblue tetrazolium NBT reduction assay. Our study indicates that AgNP exposure causes increased oxidative stress levels, the activation of p53, repression of bcl-2 and reduction of endogenous antioxidant enzymes which are involved in the mechanistic pathways of AgNPs-induced DNA damage in the Sertoli cells in vitro. This may lead to reduced numbers of Sertoli cells through promoting early spermatogonial stem cell differentiation.

Kitai Kim has completed his PhD from the Univerity of Wisconsin at Madison, and Post-doctoral studies from Childrens Hospital Boston, Harvard Medical School. He is a faculty of the Memorial Sloan-Kettering Cancer Center, affiliated with Weill Medical College of Cornell University. He has reported major publications in stem cell field including histocompatible parthenogenetic ES cells, tissue-specific epigenetic memory of iPS cells, and biological significance of redox control by ZSCAN10.

Induced pluripotent stem cells (iPSC) can be used to produce transplantable tissues. However, iPSC generated from aged donors (A-iPSC) exhibit higher genomic instability, defects in apoptosis, and a blunted DNA damage response compared to iPSC generated from younger donors (Y-iPSC). We defined the underlying mechanism as a homeostatic imbalance between reactive oxygen species (ROS) and glutathione (a ROS scavenging metabolite). Excessive glutathione activity can blunt the normal DNA damage response signalling pathway, allowing cells with genomic mutations to persist that otherwise would have been eliminated by apoptosis. We found that the pluripotent specific factor, ZSCAN10, was poorly expressed in A-iPSC, and ZSCAN10 expression allows the establishment of A-iPSC without the negative effects of aging. We found that A-iPSC have a higher level of glutathione due to excessive expression of glutathione synthetase (GSS), which causes an imbalance of ROS and glutathione. ZSCAN10 directly binds the GSS promoter to suppress GSS expression. We also found that ZSCAN10 not only controls GSS expression (to determine the total quantity of glutathione) but also glutathione peroxidase (GPX2), which suppresses the excessive catalytic activity of glutathione by controlling its transition from an oxidized inactive form to a reduced active form. We found that GPX2 is controlled by the exosome-mediated RNA degradation pathway and that ZSCAN10 expression induces RNA exosome complex expression. We found the third mechanism that ZSCAN10 controls activity of pluripotent stem cell-specific glucose transporter 3 (GLUT3) and facilitates a shift in carbon source metabolism that suppresses oxidative phosphorylation and limits ROS production, consequently providing a selective advantage for cells with elevated glutathione during reprogramming to maintain the ROS-glutathione balance. Correcting the genomic instability of A-iPSC may particularly benefit older patients who are more likely to suffer from degenerative diseases with safer transplantable tissues.

Xiufeng Zhong is a Professor and PI at Zhongshan Ophthalmic Center, Sun Yat-Sen University, China. She received her MD from Nanchang University and PhD

degree in Ophthalmology from SYSU, and did Post-doc research at Johns Hopkins University School of Medicine. Her study for the first time demonstrates that hiPSCs can generate functional retina with light-sensing photoreceptors in vitro, holding a huge promise for blindness. She has published 60 peer-reviewed papers, 8 patents. Her research has got man.

Human induced pluripotent stem cells (hiPSC) have been proven to be able to generate retinal photoreceptors responsible for sight. However, it is still unclear how closely the derivatives of hiPSC mimic the naive cells so far. Thus, this study is to see whether hiPSC-derived photoreceptors recapitulate the development of human photoreceptors in vivo. hiPSC lines from different somatic source were used in this study. Cells were cultured on MatriGel with mTeSRTM1 medium. The procedure for inducing differentiation of hiPSCs toward a photoreceptor fate was based on a previously described protocol. Differentiating human iPSCs were followed by morphological observation and characterized by immunocytochemistry and RT-PCR with molecular markers of pluripotency and/or specific for different stages of photoreceptors. Under specific differentiation conditions and multi-step induction, hiPS cells gradually acquired expression of molecular markers characteristic of different stages of photoreceptors, including cones and rods. More interesting, rods and cones situated in the outermost layer of the retinal cups, forming outer nuclear layer like in vivo counterpart. TEM showed hiPS-derived PRCs developed not only inner segments but also outer segments—a key functional structure. The timeframe for acquisition of photoreceptor was very close to that of human photoreceptor embryogenesis. Our results provide strong evidence that derivatives of hiPSCs are capable of recapitulating the molecular and cellular features of human photoreceptor differentiation in vivo. This success provides a powerful model for the study of human photoreceptor development and opens up important possibilities for disease modeling and cell therapy.

Heidi Abrahamse is the Director of the Laser Research Centre, University of Johannesburg and Department of Science and Technology/National Research FoundationmSARChI Chair for Laser Applications in Health. Her research interests include, Photobiology and Photochemistry with specific reference to photodynamic cancer therapy, stem cell differentiation and wound healing. She has supervised 40 Master’s; 15 Doctorates and 12 Post-Doctorate fellows and has published 116 accredited journal publications, 42 full paper proceedings and 11 chapters. She serves on the Editorial Boards of 8 international journals while acting as reviewer for over 40 journals. She serves as Co-Editor in Chief of the international accredited journal Photomedicine and Laser Surgery.

Cancer is a global burden, which have prompted extensive research into cancer prevention and treatment for many decades. Scientific studies have shown that a subset of cells within a tumour, called cancer stem cells (CSCs), can initiate tumour genesis. Low-intensity laser irradiation (LILI) has been applied in the treatment of numerous diseases and pathological conditions. Photobiomodulation has been shown to stimulate proliferation of cells, capillary growth, and cellular metabolism as observed by adenosine triphosphate activation. It has been shown, by using different fluences and wavelengths, LILI, can either stimulate or inhibit cellular functions. Cancer research is highly focused on improving current cancer treatments. One method of targeted cancer therapy is Photodynamic therapy (PDT), LILI, along with a photochemical compound, is used. When implementing a mechanism by which CSCs are targeted, LILI might pose as a viable treatment option. Studies have shown that using high fluences of LILI cell death may be induced in normal and neoplastic cells. In our work, lung and breast CSCs were isolated using stem cell markers and irradiated at wavelengths of 636, 825 and 1060 nm at fluences ranging from 5 J/cm2 to 40 J/cm2. Post irradiation biochemical assays were conducted to monitor cellular responses including; proliferation and cytotoxicity, after 24 hours incubation. Results indicate that LILI, when treating CSCs, can induce either a bio-stimulatory or bio-inhibitory effect depending on the wavelength and fluence used. This study indicated successful cell damage in CSCs when using HF-LILI, as well as, stimulation of ATP production, when using lower fluences of LILI.