Development of mitochondria homing drug for kidney disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08270
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tohoku University
• Principal Investigator: Suzuki Takehiro 東北大学, 医工学研究科, 准教授 (50396438)
• Co-Investigator(Kenkyū-buntansha): 豊原 敬文 東北大学, 医工学研究科, 特任講師 (60594182)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ミトコンドリア / ミトコンドリア病 / iPS細胞 / 人工血管 / 人工心筋

Outline of Final Research Achievements

Mitochondrial dysfunction causes various mitochondrial diseases and various organ　injuries (nervous systems, heart, kidney etc.). Intracellular ATP depletion and increasing mitochondria-derived reactive oxygen species (mitROS) are considered as major pathophysiologic mechanisms of disease progression in mitochondrial abnormalities. But the definitive and specific therapeutics for mitochondrial diseases have not yet been established. We established devices to access cardiac muscle, vascular and kidney injury by mitochondrial disease, using iPS cells from mitochondrial patients. 1. 96 well cardiac muscular organoid heart dynamometer(Heart-Dyno). 2. Artificial vuscular model of bilayer collagenous tube with iPS induced endothel and vusclar smooth muscles. 3. Kidney organiod of iPS induced podocytes, tubular epithelial cells and endhothelial cells.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

最も頻度の高いミトコンドリア病であるMELASは血管障害、心筋症、FSGSや尿細管障害、糖尿病など多彩な臓器障害を呈するため、MELAS患者細胞由来iPS細胞から誘導した分化細胞を用いた疾患モデルはミトコンドリア機能異常による臓器障害の病態メカニズムの解明、疾患群治療薬のスクリーニング及び治療効果判定に有用である。MELAS患者の原因遺伝子変異の80%を占めるミトコンドリア遺伝子A3243G変異患者から変異を伴うiPS細胞から分化誘導した心筋細胞の心筋評価デバイスと血管内皮及び平滑筋細胞を用いた人工血管、腎臓オルガノイドを用いてミトコンドリア障害機序の解明と治療薬の開発評価を行う。