Scientific Program

Day 1

KEYNOTE SPEAKERS
  • Cloning Barrett's stem cells suggests paths to initiation of a precancerous lesion

    National Cancer Center Research Institute
    Japan
    Biography

    Dr. Yusuke Yamamoto completed his Ph.D. in Molecular Physiology from Waseda University, Japan in 2008. He further pursued his postdoctoral studies under the supervision of Prof. Frank McKeon and A/Prof. Wa Xian at Genome Institute of Singapore. Presently, he is working as a Senior Staff Scientist at National Cancer Center Research Institute, Japan. He has been interested in how adult stem cells maintain their stemness throughout the lifespan as well as identifying cell-of-origin in esophageal adenocarcinomas and high grade serous ovarian carcinoma, which are the most aggressive type of cancers with poor prognosis. With his outstanding research work, he has published more than 40 papers in peer-reviewed journals, including Nature and Cell and holds one US patent on ‘Nanobio device of imitative anatomy structure’ in 2010 while another one, ‘Novel Diagnosis and Therapeutic Targets for Cervical Cancer’ is in the pipeline. He has presented his various research work in 15 national and international conferences and is a member of The Molecular Biology Society of Japan, Japanese Cancer Association and The Japanese Biochemical Society.

    Abstract

    Stem cell populations of columnar epithelia collectively resist cloning in their immature states. By modifying the culture technique for human intestinal stem cells, we have cultured the stem cells from precancerous lesion known as Barretts esophagus which is intestinal metaplasia, emerged from a squamocolumnar junction and would eventually evolve to esophageal adenocarcinoma. Here we report the isolation and propagation of distinct, patient-matched stem cells of Barrett's, gastric and esophageal epithelia that yield divergent tumor types following in vitro transformation and xenografting. Exome-seq revealed a broad mutational spectrum unique to Barrett's stem cells that likely reflect the risk for oncogenesis. Remarkably, 25% of cases show no cancer-related genomic changes, suggesting that Barrett's initiates without driver mutations. Most cases, however, sustain patterns of deletions almost identical to adenocarcinoma. Notably, those suspected of low-grade dysplasia have p53 mutations or undergo amplifications of proto-oncogenes and receptor tyrosine kinases, implicating these events in lethal transitions. Our findings suggest paths for the initiation and progression of Barrett's esophagus and define a discrete stem cell underlying its regenerative growth whose eradication could prevent esophageal adenocarcinoma.

  • A systems method for the complexity in regenerative medicine

    Hawaii Institute for Health and Healing LLC
    USA
    Biography

    Dr Myles Suehiro completed his graduation from University of Colorado Boulder in 1965. He is a recipient of several fellowships and certification in Internal medicine including Fellowship in Anti-Aging Regenerative and Functional Medicine. He worked as an Assistant Professor at Charles R. Drew Postgraduate Medical School till 1986, after which he was appointed as the Director of I.C.U. at City View Hospital, Los Angeles and Medical Director at Cardio-Pulmonary Lab in 1990. He holds immensely vast experience in the field of medicine (more than 45 years) and is interested in the potential of treating rare disorders with the help of regenerative and functional medicine. At present he works as the Director of the Hawaii Institute for Health and Healing, LLC.

    Abstract

    Modern medicine is based on the scientific method of observation, a hypothesis of etiology and testing that hypothesis by therapeutic trial. This method has worked well in acute diseases of a single etiology. With the success of this methodology came the sequela of chronic debilitating diseases of greater complexity with which the basic scientific method demonstrated to be difficult due to the nature of complexity. Complexity in contrast to complication refers to unpredictability and inconsistent response to a given intervention. Chronic diseases which are the focus of Regenerative Medicine are models of complexity due to their multiple interacting processes. This complexity thus demands a different methodology which would cope with the ever-changing multiple processes. A systems method or holistic approach would be an iterative, repetitive process focusing on the fundamental process of inflammation which underlies all diseases. Because inflammation has many different factors, a systematic approach to balance these underlying factors of inflammation while adjusting to the new changes ensuing from intervention must be constantly monitored. The implementation of stem cells in the chronic diseases of Regenerative Medicine would also benefit from this systems approach by decreasing the underlying inflammation and allowing the regenerative process to focus on the disorder of extreme concern. Stem cells, given intravenously, will follow the course of circulation by migrating to areas of greater inflammation. Stem cells like other cells would thrive and be more productive if placed in a stimulating environment. Therefore, the implementation of stem cells in Regenerative Medicine should be a methodical process to control generalized inflammation and allow the stem cells, by providing a stimulating environment for the better function, to focus on disorders where the conventional methods of treatment are limited.

Bioimaging Techniques | Clinical Cardiology | Advances in Regenerative Medicine and Tissue Regeneration | Clinical Research
Chair
Co-Chair

Day 2

KEYNOTE SPEAKERS
  • Applications of stem cell technology in anti- aging medicine

    Vita Stem Co. Ltd.
    Thailand
    Biography

    Dr Kampon Sriwatanakul is the president of Vita Stem Co. Ltd., Bangkok and an internationally recognized pioneer of stem cell therapy. He is currently engaged in research and development projects related to the application of mesenchymal stem cell in the anti-aging and regenerative medicine.

    Abstract

    At present there is no convincing evidence that existing “antiaging” treatments can slow aging or increase longevity. However, a variety of experiments in both animals and humans indicate that aging rates and life expectancy can be altered. General strategies that appear promising include interventions that reduce oxidative stress and cell replacement therapies can deal with specific age-related pathologies. Telomere length (TL) in blood cells is considered as a molecular marker of ageing. Circulating cell-free DNA (cfDNA) and unconjugated bilirubin (UCB) are dynamic blood constituents that need to be further explored. As we age, and in certain diseased states our cellular ability to translate a transcribed mRNA code into a functional protein, is impaired. Although the genesis of this clinical condition can be somewhat complex, it is characterized by intra-cellular protein accumulation. This accumulation not only decreases cellular function, but also impedes the translational capacity of the cell. We believe the primary etiology of this is a decrease in Chaperone Protein function inside the cell. In this paper we report that cellular aging is marked by an increase in both circulating HSP70 and cfDNA, which are significantly correlated to each other.

  • Combined therapeutic medical device and stem cells for regenerative nanomedicine.

    University of Stransbourg
    France
    Biography

    Dr. Nadia Benkirane is Research director and head of the “ Osteoarticular and Dental regenerative Nanomedicine” laboratory, at INSERM (French National Institute for Health and Medical Research), UMR 1109, Strasbourg, France. She was leader of “Active Biomaterials and Tissue Engineering” team INSERM 977. She received her Ph.D. from University Louis Pasteur, ULP, Strasbourg, France for the work on Development of pseudopeptides as synthetic vaccines. Dr. Jessel (Benkirane) then held a postdoctoral position in collaboration with the Institut Pasteur, Paris, France, working on Immunotherapy HIV, and another postdoctoral position on the application of modified peptides as vaccines against FMDV (Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944-0848, USA). She joined the INSERM U595 in 2002 as a post-doc, and received the diploma to direct the research (HDR) in 2004. Dr. Jessel got the permanent position (CR1) in the INSERM 595 laboratory in 2004 and Research Director (DR2) position in the INSERM 977 and head of “active Biomaterials and Tissue Engineering team from 2009 until 2012). Currently Research Director (DR1) in the INSERM UMR 1109 (Osteoarticular and Dental Regenerative Nanomedicine" and heads the team. Dr. Jessel possesses expertise in diverse fields of molecular and cellular biology, immunochemistry, tissue engineering and biomedical engineering. In the last 10 years, she focused her research on the bio-functionalization of multilayered polyelectrolyte architectures with emphasis on the use of these architectures to induce specific cellular responses and gain control over cell proliferation and differentiation. Dr. Benkirane-Jessel have 138 publications (h index: 36) with peer-reviewed publications in high impact factor journals (Proc. Nat. Acad. Sci. USA; Adv. Mater.; Adv. Funct. Mater.; Small; Nanoletters, Biomaterials, ACS Nano), 5 chapters reviews and 5 international patents, she is a regular referee for a number of scientific journals (Nature nanotechnology, Nature Materials, ACS nano, Biomaterials, Nanoletters…). She is under the contract (Interface INSERM/Clinic 2008-2013) and she got also “Prime d’Excellence Scientifique” from the INSERM, 2010-2014 and the PEDR from the INSERM on 2016 for 4 years.

    Abstract

    In our group we explored a new generation of smart living implants combining not only active therapeutics but also stem cells, as a novel strategy to regenerate stabilized cartilage and avoid prosthesis, by achieving regeneration of its sub-chondral bone foundation, requirement which is failing today in the clinic. A unique nanotechnology strategy is used to entrap, protect, and stabilize therapeutic agents into polymer coatings: nano-reservoirs, covering nano-fibres of implantable nano-fibrous membranes for bone and cartilage regeneration. Upon contact with cells, therapeutic agents become available through enzymatic degradation of the nano-reservoirs. As cells grow, divide, and infiltrate deeper into the porous membrane, they trigger slow and progressive release of therapeutic agents that, in turn, stimulate further cell proliferation. The nano-reservoirs technology enables to reduce the quantities of required therapeutic agent (compared to soaked membranes for instance) thereby reducing costs.

  • Stem cells and hyperbaric oxygen therapy for traumatic brain injury management

    Ain Shams University
    Egypt
    Biography

    Hazem Ahmed Mostafa is an internationally recognized neurosurgeon with over two decades of clinical and research experience. He has devoted his career to developing and providing rigorous, comprehensive and compassionate care to those with cancer, neurological degenerative diseases andpediatric disorders. He’s affectionately known as Dr Brain and Spine. He is a professor in the Department of Neurosurgery at Ain Shams University, Egypt since 2014. He is a Consultant of Neurosurgery at his own private clinics NeuroClinic Cairo and Hurghada - Red Sea, Egypt since 2001. Hazem has dedicated a significant part of his career to developing innovative educational research with over 33 published research papers in the Egyptian Society journal. Hazem is an active member of the Egyptian Society of Neurological Surgeons since 1997. He is an international Faculty at AO Trauma Foundation. He is also an international fellow member of the Institute of Brain Chemistry and Human Nutrition (IBCHNUK).

    Abstract

    Introduction: Over the past 30 years there has been a significant reduction in mortality following severe TBI together with improved outcome. This has been largely due to the use of evidence-based protocols emphasizing the correction of parameters implicated in secondary brain injury. The main parameters are cerebral blood flow, cerebral oxygenation and management of co-morbidities. Neuroinflammation is a well-established secondary injury mechanism following TBI. Methodology: Inspired by success in Parkinson’s and other neurodegenerative diseases, stem cell based therapy is believed to provide biobridges, can stabilize blood-brain barrier, reduce the oxidative stress and provide immunomodulation and neuroprotection. Hyperbaric oxygen may alleviate secondary insult in TBI through the modulation of the inflammatory response. Animal studies showed that hyperbaric oxygen improves neuroplasticity, reduce the inflammatory markers and neuronal apoptosis following TBI. Sources of stem cells: Modulating endogenous stem cells or Cell transplantation (using exogenous stem cells) from fetal/embryonic, bone marrow stromal cells, umbilical cord cells or induced pluripotent stem cells (iPSCs).There is plenty of literature showing good response of stem cell therapy, mesenchymal stem cells in particular, on the outcome in rat TBI models.The animal models indicate some vulnerability of the stem cells to the hostile environment of neuroinflammation, which may limit their potential. Conclusion: The results although very encouraging, are still in the laboratory/preclinical phase and lots of technical, ethical and logistic issues have to be solved before shifting to clinical trials. Hyperbaric oxygenation can provide less hostile microenvironment helping with repair and provide better use of stem cell induced growth factors.

Cancer Stem Cells | Nanotechnology in Regenerative Medicine | Treatment of Diseases by Stem Cell Therapies
Chair
Co-Chair
Speaker
  • The role of hematopoietic cell-derived multipotent stem cells in skin tissue repair and regeneration
    Speaker
    Yunyuan Li
    The university of British Columbia
    Canada
    Biography

    Dr. Yunyuan Li has completed his Ph.D. in 2005 from the University of Alberta, Canada. He is a currently a senior researcher at Burn and Wound Healing Research Laboratory at the University of British Columbia, Canada. His research interests were focused on the roles of hematopoietic cell-derived multi-potent stem cells in skin wound healing, hair follicle regeneration, and inflammation. Till now, Dr. Li has published over 40 articles in peer-reviewed journals.

    Abstract

    Non-healing and chronic wounds cause tremendous suffering and debilitation .To look for new strategies to improve healing of damage skin tissue and understand the mechanism underlining a complex wound healing process, in last a few years, we have conducted a serial of studies to identify healing promoting factors. We found that the macrophage colony-stimulating factor (M-CSF) released from proliferating skin cells could induce a subset of hematopoietic cells to be dedifferentiated into multipotent stem cells. Interestingly, hematopoietic cell-derived, stage specific embryonic antigen (SSEA)-1 and-3 positive, multipotent stem cells were transiently present in the wound site after skin injury. In this study, we further explored the roles of these hematopoietic cell-derived multipotent stem cells to repair injured skin and hair regeneration in a mouse model. Hematopoietic cell-derived multipotent stem cells were generated by culture mouse splenocytes in a medium containing M-CSF. Skin excisional wounds were generated by punch biopsy in mice which received nothing (control) or one million splenocyte-derived stem cells by intra-dermal or tail vein injection simultaneously. Injected stem cells expressing GFP or labeled with a fluorescent dye Dil were used for cell tracing. Immunofluorescent staining was used to identify the cell source in healing skin tissue. Results revealed that addition of M-CSF or its antibody to increase or reduce the number of hematopoietic cell-derived stem cells at the wound site could accelerate or slow skin wound healing in mice. We also demonstrated that injected hematopoietic cell-derived stem cells could be differentiated into fibroblasts, keratinocytes and blood vessel-like structures in vivo. These blood cell-derived skin cells were the major contributions of healing skin. Furthermore, our results suggested that hematopoietic cell-derived multipotent stem cells could participate in new hair follicle regeneration. In conclusion, hematopoietic cells are the major contributions and cell source for skin tissue repair and hair regeneration.

  • Platelet lysate induces chondrogenic differentiation of umbilical cord derived mesenchymal stem cells
    Speaker
    Ghmkin Hassan
    Okayama University
    Japan
    Biography

    Ghmkin Hassan obtained his master degree in biotechnology and molecular biology from Damascus University, Syria. Presently, he is a research scholar at Okayama University, japan. He was interested in isolation and optimizing stem cell culture conditions which was a part of "mesenchymal stem cell optimization culture conditions" in national commission for biotechnology Syria and his recent focus is on origin of cancer stem cells and its microenvironment.

    Abstract

    Purpose: Articular cartilage has poor repair ability and still confers a major challenge in orthopedics. Mesenchymal stem cells (MSCs) are multipotent stem cells with potential to differentiate into chondrocytes in the presence of transforming growth factor beta (TGF-?). Relevantly, platelet lysate (PL) contains many growth factors including TGF-? and ameliorates cartilage repair. Thus, we investigated the ability of PL to direct chondrogenic differentiation of MSCs along with other standard differentiation components in pellets culture system. Methods: We isolated and expanded MSCs from human umbilical cords using PL supplement medium and characterized cells by immunophenotyping and differentiation potential to adipocytes and osteocytes. We further cultured MSCs as pellets in chondrogenic differentiation medium supplemented with PL. After 21 days, pellets were processed for histological analysis and stained with alician blue and acridine orange. Expression of SOX9 was investigated by RT-PCR. Results: Although MSCs maintained their stemness characteristics in PL supplement medium, distribution of cells in pellets cultured in chondrogenic differentiation medium supplemented with PL was more similar to cartilage tissue-derived chondrocytes than negative control. In addition, intense alician blue staining indicated increased production of mucopolysaccharides in differentiated pellets, which also showed elevated expression of SOX9 detected by RT-PCR. Conclusions: Our data suggest that MSCs could be differentiated to chondrocytes in the presence of PL and absence of exogenous TGF- ?. Further research needs to be conducted to understand the exact potential role of PL in chondrogenic differentiation and chondrocyte regeneration.

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