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発表内容

Title:
Towards iPSC technology-based regenerative therapy for kidney diseases and diabetes

 

Speaker:
Kenji Osafune
Professor
Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University

 

Abstract:
Kidney diseases and diabetes cause both medical and medicoeconomical problems worldwide. Kidney, whole pancreas and pancreatic islet transplantations are an effective therapeutic strategy, but the insufficient donor organ/tissue supply is a major obstacle to these interventions. Regenerative medicine strategies using human induced pluripotent stem cells (iPSCs) are among the candidate approaches to solve the problems. Based on the knowledge of developmental biology, we are establishing the stepwise differentiation methods for kidney and pancreatic lineage cells from human iPSCs and generating kidney and pancreatic tissues from the induced cells. We are also examining the therapeutic potential of kidney and pancreatic lineage cells generated from human iPSCs by using mouse models of renal diseases and diabetes. We demonstrated that the transplantation of human iPSC-derived renal progenitors and erythropoietin (EPO)-producing cells ameliorates acute kidney injury (AKI) and renal anemia in mice, respectively. We have also succeeded in lowing blood glucose levels in diabetic mice by transplanting human iPSC-derived pancreatic cells. Towards clinical trials, we are currently developing mass culture systems for transplantable cells and transplantation methods. In this presentation, I would like to summarize the current status of kidney and pancreatic regeneration researches including our results and discuss the future perspective of iPSC technology-based regenerative treatment of kidney diseases and diabetes.

 

References:
1. Hitomi H, et al. Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice. Science Translational Medicine 9: eaaj2300, 2017.
2. Toyoda T, et al. Rho-associated kinases and non-muscle myosin IIs inhibit the differentiation of human iPSCs to pancreatic endoderm cells. Stem Cell Reports 9: 419-428, 2017.
3. Toyohara T, et al. Cell therapy using human induced pluripotent stem cell-derived renal progenitors ameliorates acute kidney injury in mice. Stem Cells Translational Medicine 4: 980-992; 2015.
4. Mae S, et al. Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells. Nature Communications 4: 1367, 2013.
5. Chen S, et al. A small molecule that directs differentiation of human embryonic stem cells into the pancreatic lineage. Nature Chemical Biology 5: 258-265, 2009.
6. Huangfu D, et al. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nature Biotechnology 26: 1269-1275, 2008.
7. Osafune K, et al. Marked differences in differentiation propensity among human embryonic stem cell lines. Nature Biotechnology 26: 313-315, 2008.