2021 Fiscal Year Final Research Report

A strategy for the rejuvenation of older donor kidney focusing the research for development, stem cell biology and kidney-bone marrow axis: The establishment of international joint research network

Research Project

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Project/Area Number	19KK0216
Research Category	Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 53:Organ-based internal medicine and related fields
Research Institution	University of Tsukuba
Principal Investigator	Usui Joichi 筑波大学, 医学医療系, 准教授 (70447340)
Co-Investigator(Kenkyū-buntansha)	川西邦夫筑波大学, 医学医療系, 助教 (00578750) 馬渕洋東京医科歯科大学, 大学院医歯学総合研究科, 助教 (50424172) 山崎聡筑波大学, 医学医療系, 教授 (50625580)
Project Period (FY)	2019-10-07 – 2022-03-31
Keywords	内科 / 臓器移植 / 幹細胞 / 老化 / 発生 / 糖鎖 / 病理学
Outline of Final Research Achievements	In this study, an international research network was established to elucidate renal aging and pathological mechanisms induced by bone marrow aging and to explore methods for rejuvenation of aged donor kidneys. Specifically, we carried out the elucidation of the mechanisms of multiorgan aging using mouse models focusing on transcription factors involved in stem cell aging, mitochondrial function changes, glycosylation abnormalities, and development (Project A) and the establishment of a verification system to attempt kidney aging and rejuvenation (Project B) based on the results of these studies. We created a validation set for aging and rejuvenation that took into account the age of the human kidney transplant donor and recipient, examined the expression of aging indicator tissues, and confirmed the possibility of rejuvenation of aging kidneys. We are now preparing to expand the system through an international network including the U.S.
Free Research Field	内科学
Academic Significance and Societal Importance of the Research Achievements	国際共同研究がアドバンテージを持つ基礎的研究課題を起案、老化に依存する幹細胞老化、ミトコンドリア機能変化、糖鎖変化、転写因子制御等と高齢者腎臓病との関連性の検討を進め、複数のインパクトのある成果を発信した。これらの基盤成果を元に骨髄移植による腎臓若返りモデル検証に研究展開できており、その成果は加齢性腎疾患（内科疾患）の発症・進展メカニズム解明に繋がる可能性が高い。続いてプロジェクトBはコロナ禍の影響から本邦の限られたサンプルでの検証となったが論文投稿に至った。高齢ドナー腎臓の若返り指標の探索、若返り手法の開発等の臨床応用を目指し国際研究展開を目指すことで更なる成果の達成が期待できる。