Pathological analysis of kidney aging and development of cell therapy using nephron progenitor cells in CKD

• Project/Area Number: 18K07043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyoto University
• Principal Investigator: Araoka Toshikazu 京都大学, iPS細胞研究所, 特定研究員 (40437661)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ネフロン前駆細胞 / 拡大培養 / 慢性腎臓病 / 急性腎障害 / 低分子化合物 / 腎臓老化 / 腎臓再生 / ヒトiPS細胞 / CKD

Outline of Final Research Achievements

The purpose is to realize cell therapies using human iPS cell-derived nephron progenitor cells (hiPSC-NPCs) for kidney diseases by developing efficient expansion culture methods for hiPSC-NPCs. We have developed expansion culture methods for hiPSC-NPCs more than 100-times and identified multiple low weight molecular compounds that increase hiPSC-NPCs by about 20-30%. Furthermore, we have identified the specific surface marker for nephron progenitor cells (NPCs) and succeeded in purifying the NPC fractions from multiple human iPS cell lines. We have improved renal function in a mouse model of acute kidney injury using expanded hiPSC-NPCs. In addition, we have improved renal function and suppressed the progression of renal fibrosis and aging in a mouse model of chronic kidney disease.

Academic Significance and Societal Importance of the Research Achievements

腎障害に対して有効な薬剤の開発は十分ではなく、慢性腎臓病患者および透析患者数は増加の一途をたどっているため、新たな治療法の開発が急務である。一方、腎疾患に対するヒトiPS細胞由来ネフロン前駆細胞(hiPSC-NPCs)の細胞療法の臨床応用に向けて、高効率かつ安価なhiPSC-NPCsの拡大培養方法の開発が課題であった。本研究において、hiPSC-NPCsの拡大培養法を開発し、急性腎障害の腎機能の改善および慢性腎臓病における腎機能の改善、腎臓の線維化および老化の進行を抑制することに成功した。これらの成果は、hiPSC-NPCsを用いた新規治療法の臨床応用の実現に向けて大きく貢献すると考えられる。