京都大学 · Biochemistry, Genetics and Molecular Biology
오사푸네 켄지 교수의 연구실은 인간 혼합줄기세포를 이용한 신장 재생의학 기반 기술을 핵심으로 하며, 특히 신장 발달의 초기 세포인 신우세포(ureteric bud), 난관형 조혈모세포(nephron progenitor) 및 중간중배엽의 유도와 분화 조절에 초점을 맞추고 있습니다. 다양한 소분자 조합과 생물학적 신호를 활용해 효율적이고 안정적인 유전자 조절을 통한 조직 재생을 목표로 하며, 특히 신장 기능을 회복시키는 데 기여하는 세포의 영양적 작용(트로픽 효과)과 관련된 분비 인자 규명에도 기여하고 있습니다. 이와 함께 인간 배아줄기세포와 유도만능줄기세포(iPSC)를 활용한 신장 유사조직(신장 오르가노이드)의 구축 및 기능적 분화 기술 개발도 핵심 과제입니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Renal stem or progenitor cells with a multilineage differentiation potential remain to be isolated, and the differentiation mechanism of these cell types in kidney development or regeneration processes is unknown. In an attempt to resolve this issue, we set up an in vitro culture system using NIH3T3 cells stably expressing Wnt4 (3T3Wnt4) as a feeder layer, in which a single renal progenitor in the metanephric mesenchyme forms colonies consisting of several types of epithelial cells that exist in
This report is the first to demonstrate that the transplantation of renal progenitor cells differentiated from human induced pluripotent stem (iPS) cells has therapeutic effectiveness in mouse models of acute kidney injury induced by ischemia/reperfusion injury. In addition, this report clearly demonstrates that the therapeutic benefits come from trophic effects by the renal progenitor cells, and it identifies the renoprotective factors secreted by the progenitors. The results of this study indi
The first step in developing regenerative medicine approaches to treat renal diseases using pluripotent stem cells must be the generation of intermediate mesoderm (IM), an embryonic germ layer that gives rise to kidneys. In order to achieve this goal, establishing an efficient, stable and low-cost method for differentiating IM cells using small molecules is required. In this study, we identified two retinoids, AM580 and TTNPB, as potent IM inducers by high-throughput chemical screening, and esta
Recent studies using human pluripotent stem cells (hPSCs) have developed protocols to induce kidney-lineage cells and reconstruct kidney organoids. However, the separate generation of metanephric nephron progenitors (NPs), mesonephric NPs, and ureteric bud (UB) cells, which constitute embryonic kidneys, in in vitro differentiation culture systems has not been fully investigated. Here, we create a culture system in which these mesoderm-like cell types and paraxial and lateral plate mesoderm-like
Ureteric bud (UB) is the embryonic kidney progenitor tissue that gives rise to the collecting duct and lower urinary tract. UB-like structures generated from human pluripotent stem cells by previously reported methods show limited developmental ability and limited branching. Here we report a method to generate UB organoids that possess epithelial polarity and tubular lumen and repeat branching morphogenesis. We also succeed in monitoring UB tip cells by utilizing the ability of tip cells to upta
The earliest form of embryonic kidney, the pronephros, consists of three components: glomus, tubule and duct. Treatment of the undifferentiated animal pole ectoderm of Xenopus laevis with activin A and retinoic acid (RA) induces formation of the pronephric tubule and glomus. In this study, the rate of induction of the pronephric duct, the third component of the pronephros, was investigated in animal caps treated with activin A and RA. Immunohistochemistry using pronephric duct-specific antibody
We generated iPSCs from patients with fulminant type 1 diabetes and differentiated them into insulin-producing cells. This in vitro disease model can be used to elucidate the disease mechanisms of fulminant type 1 diabetes.
Regenerative medicine using iPS cell technologies has progressed remarkably in recent years. In this review, we summarize these technologies and their clinical application. First, we discuss progress in the establishment of iPS cells, including the HLA-homo iPS cell stock project in Japan and the advancement of low antigenic iPS cells using genome-editing technology. Then, we describe iPS cell-based therapies in or approaching clinical application, including those for ophthalmological, neurologi
With few curative treatments for kidney diseases, increasing attention has been paid to regenerative medicine as a new therapeutic option. Recent progress in kidney regeneration using human-induced pluripotent stem cells (hiPSCs) is noteworthy. Based on the knowledge of kidney development, the directed differentiation of hiPSCs into two embryonic kidney progenitors, nephron progenitor cells (NPCs) and ureteric bud (UB), has been established, enabling the generation of nephron and collecting duct
