Day :
- Vitrification | Cell Engineering | Future of Cancer Care | Biobanking
Chair
Hiroshi Kanno
International University of Health and Welfare, Japan
Session Introduction
Hiroshi Kanno
Professor of Neurosurgery at International University of Health and Welfare School of Medicine,Japan
Title: Neuronal differentiation of skin-derived precursors by intracellular delivery of synthesized peptides derived from BC-box proteins
Biography:
Hiroshi Kanno, MD PhD is Professor of Neurosurgery at International University of Health and Welfare School of Medicine in Japan. His research interest has been focusing on stem cells and regenerative medicine for 20 years. Neuronal differentiation induction of von Hippel-Lindau tumor suppressor protein (pVHL) was found by him 18 years ago. In addition, he reported that VHL peptide mediates neuronal differentiation of stem cells. Clinical application of VHL peptide is his present theme.
Abstract:
Several somatic stem cells have potential to differentiate to neurons, and they are hopeful to be used as grafted donor cells for neuronal regenerative therapy. However, the grated cells little survive and differentiate to functional neurons in recipient neural tissue5. To overcome the problem, neural induction using neurotrophic factors or gene transfer has been employed before grafting, but neurotrophic factors do not occur specific neural induction, while gene transfer has risk of vector. If a neural induction domain for somatic stem cells exists in proteins to induce neural differentiation, its identification can contribute to neuronal regenerative therapy through neural induction of somatic stem cells using the neural induction domain. We previously demonstrated that von Hippel-Lindau tumor suppressor (VHL) protein has a function of neural induction in skin-derived precursors(SKPs) without any neurotrophic factors1. Then, we hypothesized that a neural induction domain potentially exists in the VHL protein. Here we identify a neural induction domain for somatic stem cells in the VHL protein, and show neural induction of the cells by transfer of the domain peptide linked to protein transduction domain (PTD). The neural induction domain in the VHL protein contains BC-box motif [(A,P,S,T)LXXX (A,C) XXX(A,I,L,V)] corresponding to binding site of elongin BC, which is evolutionally conserved from virus to mammalian.2,3, Therefore, we proposed that other BC-box proteins also contain the neural induction domain, and subsequently show to identify the neural induction domains at amino-acid sequences encoded by BC-box motif within BC-box proteins responsible for neuronal differentiation of somatic stem cells. In addition, we show that the domain has the same function for other somatic stem cells except for neural stem cells. Furthermore, when the domain peptide-transferred stem cells are grafted into recipient nervous tissue in neuronal disease models, the grafted cells differentiate to neurons and neuronal repair for neuronal disease models is achieved. Thus, a neural induction domain is identified at BC-box motif in BC-box proteins. The neuronal differentiation of somatic stem cells is caused by intracellular delivery of the neural induction domain peptide linked to PTD, and would contribute to neuronal regenerative therapy.
Abhijit Bopardikar
Promoter and Founder Director of ReeLabs Pvt. Ltd, Mumbai ,India
Title: Innovations in regenerative medicine that improve the results of stem cell treatment: 3D cultivation, in vivo modeling of stem cell niche, and prenatal stem cells exosomes
Biography:
Abhijit Bopardikar, MD, Promoter and Founder Director of ReeLabs Pvt. Ltd, Mumbai and Vadivarhe; Speciality Chemicals Ltd. (V.S.C.L.), Vadivarhe, Nasik, since February 2009. ReeLabs has exclusive, sophisticated, state-of- the- art technology of collecting, processing and storing stem cells from all possible human sources, outstanding R&D to further the industry and unparalleled experience of treating over 10000 cases with their proprietary therapy protocols. ReeLabs is further involved in wide range of exceptional nutraceutical products through their ‘functional foods’ division (ReeVeda) targeting several disorders naturally without side effects and niche, never-seen-before baby products through their sister concern (ReeBaby).
Abstract:
Statement of the Problem: Hair loss are currently being addressed by hair follicle transplantation. However, for large areas of alopecia, the patient does not have enough hair for auto-transplantation. Proliferation and differentiation of stem cells (SCs) requires a specific microenvironment – “stem cells niche”. For in vivo modulation of organ-specific niches during SCs transplantation could be useful fetal tissue extracts (FTEs). Exosomes are small vesicles that are secreted by various cell types, including SCs. Exosomes can be carried to distant sites via biological fluids and may therefore induce the phenotypic modifications in recipient cells. Methodology & Theoretical Orientation: Multiplying SCs of hair follicles in 2D culture and introduce them into the scalp skin to form de novo hair follicles were unsuccessful. We developed a technology for creating new hair follicles from SCs in 3D cultures. Also we investigated the content of growth factors in FTEs; and studied the efficacy of FTEs in patients who did not respond to SCs treatment. Finally, we created rejuvenation program, which includes SCs transplantation and exosomes of SCs administration. Findings: the SCs were transferred to a 3D culture where the formation of primary hair follicles suitable for transplantation occurred under the influence of a specific combination of growth factors. We showed high efficacy of using FTEs for modeling the SCs niche in treatment of liver cirrhosis and non-healing wound in patients who did not have positive response to previous SCs treatment. Transplantation of prenatal hepatoblasts, hematopoietic SCs, and fetal liver extracts administration showed efficacy in 75% of liver cirrhosis cases that was characterized by significant decrease of liver fibroscan density, decrease of portal hypertension and ascites, decrease or normalization of biochemical markers of liver damage. In patients with chronic non-healing wounds administration of FTEs activated the wound epithelialization with complete healing. Patients GAIS results after rejuvenation program: optimal cosmetic results – 78.9%; significant improvement but not complete correction – 9.7%; improvement, but required additional correction – 11.3%. The program significantly reduces the biological age, and Frailty Index that evidences about the decrease in risk of aging disease appearance. Conclusion & Significance: 3D cultivation, in vivo modeling of SCs niche and prenatal SCs exosomes can significantly improve results of the use of SCs in regenerative medicine.
A. Sotres-Vega
Lung Transplantation Research Unit, National Institute of Respiratory Diseases "Ismael Cosio Villegas" , Tlalpan, Mexico
Title: Tracheal Cartilage Cryopreservation
Time : 11:50 - 12:20
Biography:
Avelina Sotres-Vega has her expertise in cryopreserved tracheal grafts in experimental models of long segment replacement as well as teaching and learning programs on surgery using preserved biomaterials either by cryopreservation or lyophilization.
Abstract:
Currently, there are no surgical strategies to treat tracheal lesions longer than 7 cm. Such patients are not candidates for tracheal resection or end-to-end anastomosis and are thus left with only repeated palliative procedures to relieve their respiratory insufficiency. Experimental studies using cryopreserved trachea have produced contradictory results, limiting the clinical application of this technique. We evaluated the histological integrity of canine tracheal cartilage cryopreserved using two different solutions, two temperatures, and varying lengths of storage time. Thirty canine tracheal segments of 5 rings were studied. Group 1: Control without cryopreservation. Groups 2 and 4: Cryopreserved in F12K media with 20% fetal bovine serum (FBS) at -70°C for 48 hours. Groups 3 and 5: Cryopreserved in 90% FBS at -70°C for 48 hours. Groups 4 and 5 were then stored for 15 days in liquid nitrogen (-196°C). All of the segments were thawed, fixed in wax, and cut into rings. Three rings were selected for histological evaluation. Staining of cartilage matrices was significantly modified in the tracheal segments of Group 5. The central region of the cartilage ring was more vulnerable to the effects of freezing than the edges. Under the same cryopreservation temperature and storage time, tracheal cartilage integrity is better preserved when F12K media is used.
Kuang-hung Cheng
Assistant Professor at the Institute of Biomedical Sciences at National Sun Yat-sen University in Taiwan
Title: TGIF1 loss contributes to progression of KRASG12D-induced pancreatic ductal adenocarcinoma involving HAS2-CD44 activation and PD-L1 upregulation.
Time : 12:20 - 12:50
Biography:
Dr. Kuang-hung Cheng received his Ph.D. in Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA USA in 2004. His Ph.D. thesis studies focus on TGFb1/SMAD signaling in gastrointestinal diseases. He spent 5 years post-doctoral training in the Massachusetts General Hospital Cancer Center and the department of Pathology, Brigham’s and Women’s Hospital, Harvard Medical School, Boston, USA during 2004-2008. He joined National Sun Yat-Sen University (NSYSU), Taiwan as a faculty member in 2008 fall. He is now an associate professor of Biomedical Science Institute in NSYSU. He have received the Program of Excellence Award, the Ovarian Cancer Research Fund, Inc., USA in 2007. In the last decade, his laboratory has devoted to establish several genetically modified mouse models for human cancer diseases, and use those in vivo disease models to identify new therapeutic nodes for cancer treatment.
Abstract:
The identification of the TGIF1 (TG-interacting factor 1) was found to be a nuclear transcriptional corepressor of TGFb1/Smad signaling pathway. TGIF1 has been implicated in the pathogenesis of various types of human cancer, however, the prognostic role of TGIF1 is still controversial, and no role for TGIF1 has yet been indicated in pancreatic ductal adenocarcinoma (PDAC). In this study, we demonstrated that conditional deletion of TGIF1 in the mouse pancreas had no discernible effect on pancreatic development or physiology. Notably, TGIF1 loss cooperated with KrasG12D in the rapid development of PDAC in mice, with a penetrance of 100%. Moreover, we demonstrated that KrasG12D in the context of TGIF1 plus p53 loss induced PDAC with shorter latency and greater propensity for distant metastases, compared with the Pdx-1CreKrasP53L/L model. Deciphering the molecular mechanism highlighted the activation of the hyaluronan synthase 2 (HAS2)-CD44 cancer stemness pathway and upregulation of the immune checkpoint regulator PD-L1 upon TGIF1 loss in PDAC facilitate the epithelial–mesenchymal transition (EMT) and tumor immune suppression, thereby accelerating the development of PDAC metastasis. Notably, TGIF1 silencing also contributed to the alteration of the protein levels of DNMT1, HAT1 and HDAC1 in PDAC, suggesting that TGIF1 might function as an epigenetic regulator and response for aberrant EMT gene expression during PDAC progression. Ultimately, we demonstrate that targeting the HAS2 pathway in TGIF1 loss of PDAC could be a promising therapeutic strategy for improving the clinical efficacy against PDAC metastasis.
Pravin Patel
Medical Doctor at Dr.Patel's anti-aging clinic
Title: Stem cell for Diabetes and joints
Time : 12:50 - 13:20
Biography:
Dr. Pravin Patel has expertise in evaluation and passion in improving the health and wellbeing. Of patients who is being suffering chronically through the alternative medicine. His openness to accept the new development and acceptance of new innovative technologies to address the problems of the patients. His vast experience in Lifestyle related complications and age related complication. His constructive suggestions and directions create new pathways for improving healthcare. He has built these treatment strategies after years of experience in research, evaluation, and administration both in hospital US and India.
Abstract:
The stem cell technologies and the therapeutic areas are in which stem cells find many applications on challenges in clinical complication and therapy. The stem cell research and therapy is progressing Market segmented by type, technology and therapeutic area. In few countries the resolutions have been taken to accept stem cells and cell based products as Drug. In India the government has took the initiatives with the guidance of Our Prime minister to accept the as drug and various application of Stem cell therapy. The Stem cells are classified in to adult, Embryonic and cord blood. The stem cell research applied technology segmented in to cord blood banking Xeno-transplantation and organ development, repair and others applications. The therapeutic applications of stem cell research are explored to various degenerative diseases of neurology, bone and cartilage, cancer, hematology, cardiology, diabetes, dermatology hepatology and other. The geo graphical projections and estimations of progress of stem cell research is illustrated as the various regions encompassing North America, Europe, Asia-Pacific and Rest of World.
Cell and Cellular Therapies
Stem cell applications have been explored by various schools of Cell biologist and many newer applications are still under development because of the rules and restrictions of regulatory approvals of the trials and unavailability of sponsors and unacceptance of various applications. In some cases, like Arthritis Osteoarthritis, Cartilage damage spinal cord injury and heart attacks, the cells are directly injected into the damaged tissues. Significant progress has been made in understanding the challenges to successful stem cell therapy, such as the effects of age or disease on stem cell properties, altered stem cell function in Arthritis cases We observed that the reduction of pain according to the pain scale reduced drastically in patients with age group between 45-50 and above >65. Similarly we could observe Type II Diabetes cases the reduction of HbA1c 5.1+ 1 in age group of 25-45 where as age group 45-65 was 6.1+.25.
Future of Stem cells applications
By international scientific community exploration of the stem cell application for treating various diseases list has been continues to grow at a rapid pace. Stem cell has the potential to become different cell types are the key, scientists are exploring the possibility of using cord blood stem cells to treat some of the most common life-threatening diseases such as heard diseases and stroke. Now the technologies like regeneration of the organ by means of a strategy to address the problems like Shortage of organ supply in terms of Tissue matching, GVHR, Short supply of Donors, and other ethical issues. The recent technology application of 3D printing integrated technology for creating an organ using autologous stem cells will be future of Stem cell technologies.
- Tissue Repair and Regeneration | Tissue Engineering | Epigenome and Epigenetic Analysis | Biomaterials and Bioengineering
Chair
Joel I Osorio
RegenerAge International,Mexico
Session Introduction
Joel I. Osorio
CEO & Founder - Biotechnology and Regenera-tive Medicine at RegenerAge International
Title: RegenerAge System: Therapeutic effects of combinatorial biologics (Bioquantine®) and Spinal cord stimulation system on a patient with Spinal Cord section.
Biography:
CEO & Founder - Biotechnology and Regenera-tive Medicine at RegenerAge International.VP of International Clinical Development for Bioquark, Inc. Chief Clinical Officer at ReAnima™ Advanced Biosciences. Westhill University School of Medicine. Mexico.Advance Fellow by the American Board of An-tiAging and Regenerative Medicine (A4M).Visiting scholar at University of North Carolina at Chapel Hill (Dermatology).Fellow in Stem Cell Medicine by the American Academy of Anti-Aging Medicine and Universi-ty of South Florida.
Abstract:
As it has been previously demonstrated that co-electroporation of Xenopus laevis frog oocytes with normal cells and cancerous cell lines in-duces the expression of pluripotency markers, and in experimental murine model studies that Bioquantine® extract (purified from intra- and extra-oocyte liquid phases of electroporated oocytes) showed potential as a treatment for a wide range of conditions as Squint, Spinal Cord Injury (SCI) and Cerebral Palsy among others. The current study observed beneficial changes with Bioquantine® administration in a patient with a severe SCI. Pluripotent stem cells have therapeutic and regenerative potential in clinical situations CNS disorders even cancer.2-3-7 One method of reprogramming somatic cells into pluripotent stem cells is to expose them to ex-tracts prepared from Xenopus laevis oocytes1 We showed previously that coelectroporation of Xenopus laevis frog oocytes; with normal cells and cancerous cells lines, induces expression of markers of pluripotency.4 We also observed ther-apeutic effects of treatment with a purified ex-tract (Bioquantine) of intra- and extra-oocyte liquid phases derived from electroporated X. laevis oocytes, on experimentally induced pathologies including murine models of melanoma, traumatic brain injury, and experi-mental skin wrinkling induced by squalene-monohydroperoxide (Paylian et al, 2016). The positive human findings for Spinal Cord Injury, and Cerebral Palsy with the results from previ-ous animal studies with experimental models of traumatic brain injury, respectively (Paylian et al, 2016). Because of ethical reasons, legal re-strictions, and a limited numbers of patients, we were able to treat only a very small number of patients. These results indicate that Bioquan-tine® may be safe and well tolerated for use in humans, and deserves further study in a range of degenerative disorders. We propose that the mechanism of action of Bioquantine® in these various diseases derives from its unique phar-macology and combinatorial reprogramming properties. In conclusion, these preliminary find-ings suggest that Bioquantine is safe and well tolerated on patients with Cerebral Palsy and-Spinal Cord Injury, among others. In addition to the regenerative therapy and due to the patient condition, we decided to include the Restore-Sensor SureScan5-6 . Based on the of electrical stimulation for rehabilitation and regeneration after spinal cord injury published by Hamid and MacEwan 8-9 , we designed an improved deliv-ery method for the in situ application of MSCs and Bioquantine® in combination with the RestoreSensor® SureScan® Conclusions: To the present day the patient who suffered a total sec-tion of spinal cord at T12-L1 shows an im-provement in sensitivity, strength in striated muscle and smooth muscle connection, 9 months after the first therapy of cell regeneration and 1 month after the placement of RestoreSensor® at the level of the lesion, the patient with a com-plete medullary section shows an evident im-provement on his therapy of physical rehabilita-tion in standing for the first time and showing a progressively important functionality.
Elizabeth Pavez Loriè
Research Scientist in Skin Biology and In vitro modelling at Leibniz Research Institute for Environmental Medicine
Title: The use of long-term skin equivalents in research
Time : 10:45 - 11:15
Biography:
Elizabeth Pavez Loriè has her expertise in skin biology, dermatology and tissue culturing and a passion in using in vitro modeling systems to provide answers to dermatological conditions and disease, linking biology to medicine and vice versa. Her use of models started when she used in vitro models to understand the effects of retinoic acid blocking agents as well as the function of specific cytochromes in the human epidermis and additionally the first steps to use a disease model to study drug related outcomes (6, 7). She then focused on long-term skin equivalents and non-melanoma skin cancer and aging, specifically the impact of the sun on human skin, working in close collaboration with Prof. Petra Boukamp. Her goal is to provide robust and biologically accurate models to investigate the homeostatic state of the skin as well as to understand and provide the clinic with personalized testing long-term models. To do this she would like to continue developing the skin models to meet the needs of the biological/medical questions in hand.
Abstract:
An important part for the construction of skin equivalents is the living dermal compartment, which includes fibroblasts these are mainly seeded and supported by different structures (DED, collagen, Matrigel, scaffold etc). Another type of dermal equivalent, developed by Ahlfors and Billiar (2) and later adapted by Berning et al (1) among others is the cell derived matrix (cdm) model. It has no “artificial” support and is also well suited for tumor invasion studies. Here the tumorigenic cells’ behavior can be examined and their specific invasion pattern can be followed. Most skin models have a short life span and are mostly suited and used for studying acute effects, but many of the environmental agents or dermatological conditions that face the skin will not only have an immediate effect. To be able to mimic and follow conditions over a longer period of time we base our studies on stable skin equivalents that allow the generation and regeneration of epithelial tissue for up to 24 weeks (1-5), allowing us to understand the long term effects of any given alteration. The sun is one of the key environmental factors affecting
the skin with our cdm model we are able to follow the effects of chronic UV exposure for several months. We have also been able to mimic “old” skin and follow the long-term effects of experimental sunlight on this aging model. Additionally this non-immunogenic model, suits perfectly well to examine the effects of drugs such as Cyclosporin A, mimicking the skin’s condition in organ transplant recipients over a longer period of time. The use diversity makes these models great members of the skin equivalent family and hopefully they continue to contribute in studies and in the future give us an insight into the biological dimension of time.
Ronald A Nelson
Wake Forest Institute for Regenerative Medicine, USA
Title: A chemically-defined, and xeno-free cell culture medium for clinical manufacturing
Biography:
Ronald A. Nelson, Jr. earned his Ph.D in Chemistry from Wake Forest University where he designed, synthesized and evaluated the effectiveness of phosphatidylinositol 3 kinase inhibitor prodrugs in treating androgen - independent prostate cancer. Serving in over 11 different leadership roles during his graduate career, Ronald's commitment to excellence led to 4 national and 15 local awards. Passionate about research, medicine, technology, his move to the Wake Forest Institute for Regenerative Medicine was a natural fit. As a postdoctoral research fellow at WFIRM, Ronald has been the research lead for several animal surgical, microsurgical, and treatment procedures. Ronald is also the research manager for the Regen Med Development Organization (ReMDO) where he utilizes his background in analytical chemistry, cancer biology, organic synthesis, and engineering to develop universal cell culture media that is chemically-defined and xeno-free. Ronald plans to enhance this media to recapitulate the regenerative potential of cells observed in embryogenesis.
Abstract:
Background: Animal-derived biological extracts, including animal serum, are commonly used in tissue culture medium to provide bioregulatory factors that support the maintenance of cell viability and promote cell proliferation. These biological extracts are not chemically defined, are inconsistent from lot to lot, and carry the risk of disease transmission. As such, these media supplements are not optimal materials for use in clinical manufacturing processes. Our group has developed a chemically defined media based on the known constituents within the well characterized biological extract human platelet lysate. This media has been shown to provide exceptional support for most cell types derived from the mesodermal embryonic germ layer.
Methods: Human sourced or recombinant versions of the major bioregulatory factors present in human platelet lysate were added to a modified DMEM-F12 minimal medium. The factors added included platelet-derived growth factor, transforming growth factor-β, insulin-like growth factor, vascular endothelial growth factor, fibroblast growth factor, hepatocyte growth factor, epidermal growth factor, and several other factors. Growth curves for an extensive panel of commercially available human primary cells were generated using an IncuCyte S3 Live Cell Imager. Preservation of cell phenotype was confirmed by immunofluorescent determination of cell type specific functional proteins.
Results: Proliferation rates for most mesoderm derived cell types in the chemically defined medium were equivalent or superior to proliferation rates measured in the cell supplier’s recommended, chemically undefined medium. Preservation of functional biomarker expression indicated that cell phenotype was maintained across multiple cell passages for each cell type. However, two endothelial cell types, human umbilical vascular endothelial cells and human dermal microvascular cells, did not proliferate in the chemically defined medium.
Conclusion: A chemically defined cell culture medium based on the known constituents of the biological extract, human platelet lysate was formulated using human sourced and recombinant protein bioregulatory factors. This media formulation was shown to support proliferation and preservation of phenotype for most cell types of mesodermal origin. Because this medium is chemically defined and xeno-free, it represents an optimal reagent for use in clinical manufacturing processes.
Lisa M. Domke
PhD student in the Helmholtz Group for Cell Biology
Title: The seminiferous tubules of mammalian testes: A different epithelium encased by a bandage structure of smooth muscle cell monolayers
Time : 12:05-12:35
Biography:
Lisa M. Domke is a PhD student in the Helmholtz Group for Cell Biology of Professor Werner W. Franke (German Cancer Research Center, DKFZ, Heidelberg, Germany). Before she has prepared her master thesis with one of the pioneers in cancer research, Prof. Dr. Robert A. Weinberg, at the Massachusetts Institute of Technology (MIT) in Cambridge, USA. The nature of her degree in Biotechnology has allowed her to learn various analytical as well as light and electron microscopical techniques and to work in different fields of life sciences. At present she is finishing her thesis at the DKFZ with Prof. Dr. Werner W. Franke on the molecular and ultrastructural characterization of cell-cell junctions and cytoskeletons in the tubuli seminiferi and their encasing contractile peritubular wall smooth muscle system of diverse mammalian species to improve current methods of molecular diagnostics.
Abstract:
Mature seminiferous tubules (STs) of mammalian testes comprise the Sertoli cells and germ cells and are tightly surrounded by a special peritubular cell wall. Using biochemical, immunocytochemical and electron microscopical methods, we have determined that STs differ from all other epithelia by the absence of cytokeratin intermediate filaments (IFs) but are rich in vimentin IFs, do not contain major epithelial marker structures and molecules such as desmosomes or E-cadherin-based adherens junctions (AJs) but contain exclusively N-cadherin-based AJs. In Sertoli cells, we have found two new junction structures:(i)N-cadherin-based areae adhaerentes which often represent even very large areas connecting Sertoli cells with each other or with germ cells. (ii) Special AJs arranged in closely and regularly spaced rows of tight junction-like structures and associated with 5-8 nm wide cytoplasm-to-cytoplasm channels(“cribelliform junctions”).
The seminiferous tubule cells are attached to the peritubular wall by a well-developed basal lamina but lack hemidesmosomes and hemidesmosomal marker molecules. The peritubular wall is a stack system of layers of extracellular matrix (ECM) structures alternating with monolayers of very flat “lamellar smooth muscle cells” (LSMCs). These LSMCs represent differentiated smooth muscle cells (SMCs; positive for smooth muscle α-actin, the corresponding myosin light and heavy chains, α-actinin, tropomyosin, smoothelin, desmin, vimentin, filamin, talin, dystrophin, caldesmon, calponin and protein SM22α). The cells are laterally connected – often in overlapping protrusions – by AJs containing cadherin-11 as the predominant cadherin, and also P-cadherin and rarely N-cadherin, anchored in cytoplasmic plaques containing β-catenin, proteins p120 and p0071, plakoglobin and protein myozap. LSMCs also contain typical SMC structures such as “dense bodies”, plasma membrane-associated “focal adhesions” and caveolae. Thus, we conclude that these LSMCs represent a specific SMC type and not just “myoid cells” or myofibroblasts as stated in the literature.
Biography:
Ching-Chieh Weng has his expertise in evaluation and passion in creating new Genetically Engineered Mouse Models. In his Ph.D training, he used cre-loxp system to build a lot of cancer models, such as pancreatic cancer, prostate cancer and Glioblastoma Multiforme. And Tring to Find a new treatment can replace the traditional drug therapy. He has built these cancer model after years of experience in research in hospital and education institutions.
Abstract:
Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy, which is characterized by activating Kras mutations and inactivation of the p53-Arf pathway in virtually all cases. Krüppel-like transcription factor 10 (KLF10), also referred to as TIEG1, plays essential roles in mediating TGFβ signaling and has been shown to function as a tumor suppressor in multiple cancer types. However, its roles in mediating cancer development and progression in vivo have yet to be fully characterized. Here, we have employed two well-characterized Pdx-1Cre LSL-KrasG12D and Pdx-1Cre LSL-KrasG12D p53L/L PDAC models to ablate KLF10 expression and determine the impact of KLF10 deletion on tumor development and progression. We demonstrate that loss of KLF10 co-operates with KrasG12D leading to an invasive and widely metastatic phenotype of PDAC. Mechanistically, loss of KLF10 in PDAC is shown to increase distant metastases and cancer stemness through activation of SDF-1/CXCR4 and AP-1 pathways. Furthermore, we demonstrate that targeting the SDF-1/CXCR4 pathway in the context of KLF10 deletion substantially suppresses PDAC progression suggesting that inhibition of this pathway represents a novel therapeutic strategy for patients with this disease
Sang Wook Kang
DMD, Dankook University, Republic of Korea
Title: Genetic Variants Associated with Changes of Body Mass Index in Korean Adults from Anseong/Asan cohort
Biography:
Kang has expertise in oral pathology. Based on his years of clinical and research experience, he is conducting research on diseases that can affect the dental field. He is currently focusing on genetic-based research using next generation sequencing.
Abstract:
While studies in the past have responded to the growing epidemic of obesity by examining the relationship between obesity and genetics, little research has been done on the connection between obesity and long-term changes in body mass index (BMI). The purpose of the present study is to investigate the relationship between the changes of BMI and genetic polymorphisms. In order to examine this relationship, the 10,030 cases of the Anseong and Ansan cohorts were collected from the Korean Genome and Epidemiology Study (KoGES) conducted by the Korean National Institute of Health between 2000 and 2014. Cases were withdrawn if they did not provide information on the subject’s BMI throughout the study, which finally resulted in a sample size of 3,074 cases. Their genetic data were obtained using HumanExome BeadChip which included 242,901 polymorphisms. Relationship between changes of BMI and genetic polymorphisms was examined using PLINK and STRING and DAVID program was performed for function study. For each group, statistically significant differences were confirmed in AEN, ANKS1B, CSF1, EEF2K, FRAS1, GRIK4, PDGFC, THTPA and TREH, and a clustering of genes associated with the pathway of type 2 diabetes, cardiovascular disease, and metabolic pathways were discovered. These results show that specific genetic variants are associated with increases and decreases in BMI.
- Special Session
Session Introduction
Yijia Li
Director, Shunxi Stem Cell and Regenerative Medicine Research Center,Yunnan Province Stem Cell Bank,China
Title: China is Marching into Stem Cell Era
Time : 14:30 - 15:10
Biography:
Dr. Yijia Li has a bachelor degree of biology from Tsinghua University and double degree of Economics and Management from Peking University. After his Ph.D. at Florey Institute of Neuroscience and Mental Health, he joined Shunxi-Monash University Joint Lab, participated and facilitated several translational projects with Monash University, University of Melbourne, RMIT, CSIRO, ARC and NHMRC. In 2015, he was appointed as the director of Yunnan Province Stem Cell Bank (YSCB) and Yunnan Shunxi Stem Cell and Regenerative Medicine Research Center (SSRC). YSCB and SSRC has around 1600 m2 GMP lab space can hold up to 400,000 stem cell samples and can do 200 Human Whole Exome Sequencing every week. He leads several projects is MSC basic and translational research in both China and Australia with fund up to nearly 2 million USD and has translated several books into Chinese including 5th Edition of NetCord-FACT Cord Blood Accreditation Manual.
Abstract:
China holds the stem cell treatment is the future and supports various basic and translational research. In 2015, Central Government has three policies released and In March 2016 founded the Stem Cell Translational Committee with 33 Scientific members. June 2016, China approved 30 hospitals to carry out stem cell translational research and the final stem cell treatment will be using a new registration pathway. Dec 2017, second batch, 72 certified hospitals released. Therefore, open the gate of many stem cell clinical trials.
Now stem cell development especially MSC development is moving very fast. It is estimated that in the next 3-5 years, China will approve several stem cell treatments and also support hundreds of translational research
- Stem Cells | Anti-Aging and Regenerative Medicine | Personalized Medicine | Future of Cancer Care
Chair
Abhijit Bopardikar
ReeLabs Pvt. Ltd., India
Session Introduction
A. Sotres-Vega
Lung Transplantation Research Unit, National Institute of Respiratory Diseases "Ismael Cosio Villegas" , Tlalpan, Mexico
Title: Cryopreserved and lyophilized organs in surgical skills training
Time : 15:10 - 15:40
Biography:
Avelina Sotres-Vega has her expertise in cryopreserved tracheal grafts in experimental models of long segment replacement as well as teaching and learning programs on surgery using preserved biomaterials either by cryopreservation or lyophilization.
Abstract:
Developing surgical skills is essential in the training of all the surgical specialties. However, ethical, legal, and economic issues have limited surgical training associated with learning on human patients, human cadavers and live laboratory animals. Cryopreservation and Lyophilization are two techniques that preserve the structure and function of tissues and cells. We have developed training programs to teach surgical skills to junior surgeons based on experimental animal organs preserved either by cryopreservation or lyophilization and we have obtained excellent results. 1) Cryopreservation: a) Thirty stomachs were harvested from Wistar rats at the end of non-abdominalresearch studies. The stomachs were washed with cold saline solution and filled with hyaluronic acid solution.The organs cryopreserved at -30°C for 60 days. The stomachs were thawed to room temperature on the day of the surgical skills practice and two full-thickness incisions were made. b) Ten tracheas were harvested from ten non-trachea related research dogs at the moment of euthanasia. Tracheas were trimmed in six or seven rings segments and cryopreserved at -70°C for 60 days during 60 days. The day programmed for surgical skills practice, they were thawed to room temperature. Two incisions were made on every tracheal segment and sutured with running or separate stitches. 2) Lyophilization: Esophagus were harvested from four non-esophagus related research dogs at the moment of eutanasia and trimmed in 3 cm long segments. They were lyophilized at -55ºC and 10 mBar vacuum pressure during 24 hours. The day programmed for surgical skills practice, they were rehydrated. One incision was made on every esophageal segment and sutured with running stitches. Preservation of different tissues is a practical, reproducible,low-cost, and high-fidelity bench model that allows surgical fellows to learn how to handle an organ and improve their surgical abilities before performing surgery on patients or laboratory animals.
Mindy Min-sun Oh
CEO of bBHC and STC Stem Cell Treatment & Research Institute
Title: Newly Elicited Pluripotent Stem Cell
Time : 16:30- 17:00
Biography:
Mindy Minsun oh is currently the CEO of bBHC and STC Stem Cell Treatment & Research Institute. She had finished her AAS degree from Fashion Institute of Technology and Her Bachelor's degree in Business Management from Sang Myung university. She also Copyright holder of Patent related to newly Elicited Pluripotent stem cells.
Abstract:
Introduction of nEPS
nEPS (Newly Elicited Pluripotent Stem Cell by Natural Compound) is a pluripotent stem cell to induce pluripotency from separating human mesenchymal stem cell (hMSC). MSCs are cultured and then treated with small molecular compound extracted from natural products (plant). In that case, MSCs can form many colonies. This stem cell colony have expression of protein and DNA gene, only found in pluripotent stem cell, and it can be differentiated into all cells that constitute human body including ectodermal, endodermal and mesodermal cells. Adult stem cell can only be differentiated into cells of a specific tissue, but pluripotent stem cell has a core advantage as a cell therapy product that can be differentiated into cells of all human bodily tissues. nEPS uses stem cell separated from adult tissues like umbilical cord and fat tissue, shows significantly short time for production with production efficiency over 90%, and has no tumor occurrence caused by mutation of gene sequence from gene manipulation. In addition, STC-nEPS accompanies an advantage that it can be used on anyone without immunological rejection.
Conclusion
The application of pluripotent stem cells that has received the most attention in recent years is as a novel source of cells for cell replacement therapy for the treatment of a wide range of incurable diseases. As shown above, DNA analysis has confirmed that nEPS is pluripotent stem cell without tumor occurrence. Also, we successfully differentiated stem cell into human pancreatic beta cell, neurocyte, hepatocyte, chondrocyte, osteoblast and kidney cell.
Seok Woo Yang
The J Company, Republic of Korea
Title: Personalized nutrition therapy, in Hashimoto’s thyroiditis and herpes zoster oticus, recalcitrant to conventional therapy
Biography:
Seok Woo Yang has worked as a primary Physician and Clinical Director of the Yonsei MokGu Clinic, South Korea. He has been studying the pulse pattern diagnosis (PPD) of the radial artery in the wrist in the clinical field. He has established a plausible but applicable concept of PPD in terms of diagnostic medicine, with this result of PPD, he has established the analytic algorithm of a blood test to prescribe personalized nutritional therapy in disease entities recalcitrant to conventional therapy.
Abstract:
Personalized nutrition therapy (PNT) has been developing in terms of functional medicine. Its efficacy has been controversial. In the scope of functional medicine, the diagnostic methods to analyze blood are generally based on two kinds of perspectives: (1) Biochemistry and (2) Blood chemistry and CBC with differential counts. Out of two methods, I devised the latter of my own with imbibing the result of my pulse pattern diagnosis. The pulse pattern diagnosis established by me can measure the metabolic, inflammatory and/or hemodynamic states of major organs, using the radial artery in the wrist of each person. For example, when hepatobiliary tract cells are metabolically activated and/or liver is hyper-perfused, my pulse pattern diagnosis indicates correlation with the increased value of uric acid in blood analysis. The effect of vitamin B5 on liver decreases the metabolic rate and blood flow into liver in terms of my pulse pattern diagnosis. It has been reported that vitamin B5 is important in breaking down the excess of uric acid in our body. Likewise, my blood analytic algorithm for PNT is created. I have four clinical records of two kinds of disease entities: (1) Herpesoticus with acute otitis media and (2) Thyroid Hashimoto’s thyroiditis. In herpesoticus it was one case where a woman with acute otitis media with a history of recurrent chronic otitis media and its ear operation. She was recalcitrant to two antibiotics prescribed by antibiotic sensitivity test, performed in one university hospital. With this situation, she visited and I analyzed blood testing in terms of my personalized nutrition therapy. After taking in the prescribed PNT for 47 days, as the photo for ear tympanic membrane shown, the exudate of otitis media was remarkably vanished. In thyroid Hashimoto’s thyroiditis there were three cases. The same method was applied to three cases of Hashimoto’s thyroiditis. The results showed a decrease of TMTPO Ab titers ranging from 70.8 to 80.4%. In summary, PNT may be an alternative to the invincible infectious and autoimmune diseases recalcitrant to conventional therapy.
- Exhibitor Session
Session Introduction
Romuald Vally
Alveole, France
Title: Orchestrating the topography and chemistry of cell microenvironment with contactless and mask-less quantitative photo-patterning
Biography:
Romuald Vally is the CEO of Alveole, has been In-Charge of Alvéole’s Management and Development since 2016. He has acquired 10 years of professional experience mixing manufacturing and distributing medical equipment; first at Echosens and then at SEBAC.
Abstract:
Cell biology is faced with significant challenges when attempting to create complex microenvironments to unravel intricate mechanisms involved in cell functions, cell and tissue development, cell adhesion, cell polarity, cell migration etc. These challenges can be overcome by molecular printing which involves the controlled deposition of molecules on a substrate at the micrometer scale. These approaches have developed tremendously in the past few years and micropatterned substrates are now routinely used for biological research. To yield biologically relevant data, printed biomolecules should mimic the complexity of the in vivo microenvironment. Micrometer-scale gradients of multiple proteins are thus highly desirable. Here we present PRIMO custom micro-patterning system for cell control which allows controlling the chemistry and topography of the cellular microenvironment and studying their impacts on cell development. This contactless and mask-less quantitative multi-protein photo-patterning solution is based on the light-induced molecular adsorption of proteins (LIMAP) technology. The PRIMO system combines a UV illumination module and a specific photoactivatable reagent (PLPP). The combined action of UV-light and PLPP locally degrades antifouling polymer brushes allowing for the adsorption of proteins in a well-defined area. PRIMO relies on a wide-field DMD-based projection system coupled to an epi-fluorescence microscope to project custom-defined patterns of UV light onto all standard cell culture surfaces. As a result, micrometer scale patterns are generated within seconds. The remaining background allows for the sequential patterning of multiple proteins. Controlled protein gradients of custom-defined shape can also be patterned. In addition, PRIMO technology allows for micro-fabrication by photo-polymerization of UV-sensitive materials and also protein patterning onto pre-existing 3D surfaces. This new micro-patterning technology empowers biomedical research in neurobiology, immunology, stem cell biology, oncology and tissue engineering.