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SELECTBIO Conferences Stem Cells for Drug Discovery & Toxicity Screening 2017

Ryuji Morizane's Biography

Ryuji Morizane, Associate Biologist, Renal Division, Brigham and Women’s Hospital Affiliated Faculty, Harvard Stem Cell Institute

Dr. Morizane has earned an M.D. in 2005 as well as a Ph.D. in 2011 at Keio University School of Medicine in Japan. He has a long-standing interest in translational research using pluripotent stem cells especially for genetic kidney diseases and drug discovery, and understanding mechanisms of kidney injury, repair and fibrosis. He has been working on pluripotent stem cell research since 2007 when he became a graduate student at Graduate School of Keio University in Japan. He identified growth factors and transcriptional factors to promote the differentiation of pluripotent stem cells into kidney lineage cells, and published several publications related to kidney differentiation from pluripotent stem cells, kidney injury and fibrosis, or rare kidney diseases. He came to the USA in 2012, and has spent three years conducting scientific research in kidney differentiation from human pluripotent stem cells during a postdoctoral fellowship at Brigham and Women’s Hospital, Harvard Medical School. He worked with researchers from Harvard Stem Cell Institute, and contributed to establishment of the differentiation protocol from human pluripotent stem cells into intermediate mesoderm cells and proximal tubule-like cells. Then, he obtained a faculty position as Associate Biologist and Instructor at Brigham and Women’s Hospital and Harvard Medical School in 2015. To further facilitate the differentiation of human pluripotent stem cells into kidney lineages, he redesigned the differentiation approach where he precisely followed in vivo kidney development. He established a protocol to induce nephron progenitor cells with nearly 90% efficiency within 8~9 days of differentiation, which subsequently differentiated into nephron (kidney) organoids with multi-segmented nephron structures. This novel system has great potential for studies on kidney disease, nephrotoxicity of drugs, and kidney regeneration. He received Research Excellence Award at Discover Brigham in 2015 and Career Development Award at Brigham and Women’s Hospital in 2016.

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Kidney Organoids for Drug Discovery and Toxicity Screening

Tuesday, 11 July 2017 at 11:00

Add to Calendar ▼2017-07-11 11:00:002017-07-11 12:00:00Europe/LondonKidney Organoids for Drug Discovery and Toxicity ScreeningStem Cells for Drug Discovery and Toxicity Screening 2017 in Boston, USABoston,

We have developed an efficient, chemically defined protocol for differentiating human embryonic stem (ES) cells and induced pluripotent stem cells (iPSCs) into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro we generate SIX2+SALL1+WT1+PAX2+ NPCs with 80-90% efficiency within 8-9 days of initiation of differentiation. The NPCs form PAX8+LHX1+ renal vesicles that self-organize into nephron structures. NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle and distal nephrons in an organized, continuous arrangement that resembles the nephron in vivo. The organoids express genes reflecting many transporters seen in adult metanephric-derived kidney as well as important kidney endocrine genes such as the gene responsible for the production of erythropoietin. Stromal cells are also generated with the presence of PDGFRß+ (pericyte), endomucin+ (endothelial cell), or a-SMA+ (myofibroblast) interstitial cells. The entire procedure is performed with completely defined conditions without the need for embryonic spinal cord. This kidney differentiation system can be used to study mechanisms of human kidney development. Organoids can be used to evaluate nephrotoxicity of drugs as we have shown the expression of Kidney Injury Molecule-1 in structures that express markers of proximal tubules after exposure to nephrotoxicants. Glomerular toxins alter the cytoskeletal distribution of the glomerular structures. Epithelial toxins and TGFß can cause increased of stromal cells with characteristics of myofibroblasts. Hence the generated kidney organoids are effective tools to study genetic disorders of the kidney as well as mechanisms of toxicity. Generation of NPCs, when coupled with tissue engineering, may lead the way to generation of functional kidney replacement tissue in the future.

Add to Calendar ▼2017-07-10 00:00:002017-07-11 00:00:00Europe/LondonStem Cells for Drug Discovery and Toxicity Screening 2017Stem Cells for Drug Discovery and Toxicity Screening 2017 in Boston, USABoston,