Elucidation factors of self-vascularization in human renal organoid

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K12763
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Sekiya Sachiko 東京女子医科大学, 医学部, 非常勤講師 (00398801)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 腎オルガノイド / 血管化 / メカニカルストレス / pericyte

Outline of Final Research Achievements

The self-vascularization of renal organoid-derived human iPS cells was few that contributed to a glomerular vasculature in vivo after transplantation. Therefore, this study aims to elucidate factors of self-vascularization in human renal organoids by focusing on pericytes derived from organoids and mechanical stress. The result indicated endothelial cells derived from renal organoid expressed genes which specific renal vasculature. Moreover, these endothelial cells maintained their proliferation by the secretion factor from mesenchymal cells in renal organoids. Furthermore, culture medium perfusion also stimulates pre-vasculature structure in renal organoids. Thus, the self-vascularization factor of renal organoids was both the co-cultured cells and mechanical stress in culture conditions.

Free Research Field

再生医工学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は腎オルガノイド内部に誘導される血管ソースの重要性とその活用のためのメカニカルストレスの必要性を示唆した。PericyteはPDGF-PDGFRを介して血管内皮細胞に作用し、維持に必須であり、さらには血管内皮細胞もしくはpericyteへのかん流刺激に応答するPEZOやplexin等の因子がこれらの発達に不可欠であることが推測され、今後の生体内外での腎オルガノイドの成熟化に需要な知見が得られた。また、これらは生体外での腎血管に対する薬剤試験モデルの開発や、腎血管に関わる病態解明・治療開発研究への発展が期待される。