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発表内容

Title:
Directed Differentiation of iPSCs/ESCs into Kidney Lineages towards Clinical Application

Kenji Osafune, M.D., Ph.D.
Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University , Kyoto , Japan ,

Abstract:
Chronic kidney disease (CKD) causes both medical and medicoeconomical problems worldwide. Regenerative medicine strategies using induced pluripotent stem cells (iPSCs) are among the candidate approaches to solve the problems. Cell replacement therapy and disease modeling with patient-derived iPSCs should be examined for CKD. The mechanisms of kidney morphogenesis and cell fate determination of renal lineage cells have been elucidated by using experimental animal models. Based on the knowledge of kidney development, considerable work has already been carried out with regard to the generation of renal lineage cells from mouse embryonic stem cells (ESCs), whereas few reports have described the research on kidney regeneration using human ESCs or iPSCs. We have recently established highly efficient differentiation methods from human iPSCs/ESCs into intermediate mesoderm, an embryonic germ layer that gives rise to most cells constituting adult kidney, with an induction rate of more than 90%. These human mesoderm cells show the developmental potential to differentiate into multiple renal cell types and to form three-dimensional renal tubular structures. We are currently working on the development of the induction protocols from human iPSCs/ESCs into renal progenitor cells through the intermediate mesoderm cells. Further elucidation of the mechanisms of kidney development and establishing the method for directed differentiation from human iPSCs/ESCs into renal cells will be required for the development of iPSC technology-based treatment for CKD. I would like to summarize the current status of regenerative medicine research for CKD including our results and describe the future perspectives.

References:
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2. Osafune K. iPS cell technology-based research for the treatment of diabetic nephropathy .Seminars in Nephrology 32: 479-485, 2012.

3. Chen S, Borowiak M, Fox J, Maehr R, Osafune K, Davidow L, Lam K, Peng L, Schreiber S, Rubin L, Melton DA. A small molecule that directs differentiation of human embryonic stem cells into the pancreatic lineage. Nature Chemical Biology 5: 258-265, 2009.

4. Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2.Nature Biotechnology 26: 1269-1275, 2008.

5. Osafune K, Caron L, Borowiak M, Martinez RJ, Fitz-Gerald CS, Sato Y, Cowan CA, Chien KR, Melton DA. Marked differences in differentiation propensity among human embryonic stem cell lines. Nature Biotechnology 26: 313-315, 2008.