Analysis of vascular invasion in xenogeneic metanephros transplantation for kidney regeneration.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17258
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Matsumoto Kei 東京慈恵会医科大学, 医学部, 助教 (30439799)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 再生医療 / 慢性腎不全 / 異種移植 / 血管侵入 / 後腎移植

Outline of Final Research Achievements

In our study, kidneys in the developmental stage are transplanted for renal regenerative medicine．　In order for the new kidney to function efficiently, recipient blood vessels with sufficient blood flow need to be drawn into the new kidney, but blood flow by the invading vessels has been insufficient so far. In this study, we examined whether vascular endothelial growth factor (VEGF) improves vascular invasion into the new kidney in a rat model. In the VEGF group, the maximum diameter of invading vessels was increased by about 2-fold, the number of invading vessels increased, and the corticomedullary boundary became clearer. Next, HIF-PH inhibitors were administered to the recipient rats for comparison. The results showed that the HIF-PH inhibitor group tended to have larger kidneys and larger tubular lumens. Additional studies are currently underway.

Free Research Field

腎臓再生医療

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病は8人に1人の国民病と認知され、日本における患者数は1330万人にのぼる。現在日本国内に約35万人の透析患者がおり、腎臓再生医療の開発は喫緊の課題である。本研究は腎臓再生医療を開発する上で、移植した幼弱腎をより大きくするために、より良い血管侵入をもたらすために遂行した。その結果、VEGFを使用するとより良い傾向が得られたため、VEGFを誘導する作戦として、近年ヒト臨床に上市されているHIFーPH阻害薬を投与することに着想し、実際に腎臓の一部のサイズや機能を大きくすることに成功した。統計学的有意差を得るために現在追加実験中であるが、腎臓再生医療実現へ一つ歩を進めることができた。