Mitochondria transfer by highly-purified MSC in mitochondira diseases

• Project/Area Number: 18K15673
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Shimane University
• Principal Investigator: Misaki Matsumura 島根大学, 医学部, 客員研究員 (30811244)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 間葉系幹細胞 / ミトコンドリア病 / ミトコンドリア 病 / 間質細胞

Outline of Final Research Achievements

To clarify that the transfer of mitochondria from high-purity mesenchymal stem cells (REC )with extremely high mitochondrial content restores the cell function of mitochondrial disease for which there is no cure, mitochondrial function was investigated by co-culturing with REC using mitochondrial deletion cell line (ρ0 cell line) and nerve cells differentiated from iPS cells derived from patients with mitochondrial disease. Both cells have better mitochondrial transfer efficiency from REC compared with mesenchymal stem cells established by conventional culture methods. Recovery of mitochondrial membrane potential and ATP production ability and decrease in active oxygen. and lactic acid was observed.

Academic Significance and Societal Importance of the Research Achievements

高純度間葉系幹細胞は増殖だけでなく遊走性に優れていることは証明している。また、非臨床POCにおいて、静脈内の反復投与での安全性も実証済みであることから、有効性が得られれば可及的速やかに臨床試験あるいは治験を行うことができるため、臨床応用が可能な細胞である。ミトコンドリア病に対する確立した治療法が存在しない現在、今回の高純度間葉系幹細胞がミトコンドリア移入に優れているだけでなくミトコンドリア機能も回復させることから、今後in vivoでの有効性が実証できれば世界初の有効な治療法となり得る可能性が高い。