Intractable disorders arising in kidney, pancreas and liver, such as chronic kidney disease (CKD), diabetes and liver cirrhosis, cause both medical and medicoeconomical problems worldwide. In order to overcome these problems, our laboratory is focusing on the in vitro differentiation of kidney, pancreas and liver cells from human iPSCs and the tissue or organ reconstruction from the induced cells for transplantation therapy. We are also developing iPSC-based disease models to discover drugs for the intractable disorders of kidney, pancreas and liver.
Research and Education
By establishing the directed differentiation methods from human iPS cells into kidney, pancreas and liver lineage cells, our group is working on the following projects 1) the mechanistic elucidation of organogenesis of kidney, pancreas and liver 2) the development of cell therapy and reconstruction of transplantable organs for CKD, diabetes and liver cirrhosis and 3) the creation of disease models and drug discovery for intractable disorders of kidney, pancreas and liver, such as polycystic kidney disease (PKD), Alport syndrome, hereditary diabetes and pancreatitis and non-alcoholic steatohepatitis (NASH).
Figure 1. Kidney tissues generated from human iPS cells. Immunostaining or lectin staining for glomerular podocytes (PODOCALYXIN; white), proximal renal tubules (Lotus tetragonolobus lectin, LTL; red) and distal renal tubules (CDH1; green) (Tsujimoto H. et al., 2020).Figure 2. Pancreatic islet tissues generated from human iPS cells. Immunostaining for pancreatic β cells (INSULIN; red), α cells (GLUCAGON; green) and nuclei (blue) (Kimura A. et al., 2017).
- Tsujimoto H, Kasahara T, Sueta SI, Araoka T, Sakamoto S, Okada C, Mae SI, Nakajima T, Okamoto N, Taura D, Nasu M, Shimizu T, Ryosaka M, Li Z, Sone M, Ikeya M, Watanabe A, Osafune K. A modular differentiation system maps multiple human kidney lineages from pluripotent stem cells. Cell Reports, 2020; in press.
- Hitomi H, Kasahara T, Katagiri N, Hoshina A, Mae SI, Kotaka M, Toyohara T, Rahman A, Nakano D, Niwa A, Saito MK, Nakahata T, Nishiyama A, Osafune K. Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice. Science Translational Medicine, 2017; 9(409). pii: eaaj2300.
- Toyoda T, Kimura A, Tanaka H, Ameku T, Mima A, Hirose Y, Nakamura M, Watanabe A, and Osafune K. Rho-associated kinases and non-muscle myosin IIs inhibit the differentiation of human iPSCs to pancreatic endoderm cells. Stem Cell Reports, 2017; 9(2): 419-428.
- Toyohara T, Mae SI, Sueta SI, Inoue T, Yamagishi Y, Kawamoto T, Kasahara T, Hoshina A, Toyoda T, Tanaka H, Araoka T, Sato-Otsubo A, Takahashi K, Sato Y, Yamaji N, Ogawa S, Yamanaka S, Osafune K. Cell therapy using human induced pluripotent stem cell-derived renal progenitors ameliorates acute kidney injury in mice. Stem Cells Translational Medicine, 2015; 4(9): 980-992.
- Mae S, Shono A, Shiota F, Yasuno T, Kajiwara M, Gotoda-Nishimura N, Arai S, Sato-Otubo A, Toyoda T, Takahashi K, Nakayama N, Cowan CA, Aoi T, Ogawa S, McMahon AP, Yamanaka S, Osafune K. Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells. Nature Communications, 2013; 4: 1367.
LaboratoryProfessor Kenji Osafune