Establishment and functional analysis of IGF-2 positive iPSC-derived cardiac progenitor cells as a novel tool for cardiac cell transplantation

• Project/Area Number: 17K15981
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Asahikawa Medical College
• Principal Investigator: Aonuma Tatsuya 旭川医科大学, 医学部, 助教 (90646001)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 再生医療 / iPS細胞 / 心筋前駆細胞 / 心筋分化 / 移植・再生医療 / 心筋再生 / IGF-2

Outline of Final Research Achievements

The aim of this research is to establish iPSC-derived cardiac progenitor cells which have superior capability of cardiac differentiation and to assess therapeutic effect of the iPSC-derived cells by transplanting into mouse myocardial infarction models. Based on our preliminary data that cardiac progenitor cells-derived iPSC which have high superior capability of cardiac differentiation had higher expression levels of IGF-2, we purified IGF-2 positive cells from cardiac differentiated iPSCs. We demonstrated that purified iPSC-derived IGF-2 positive cells have superior capability of cardiac differentiation. We established the method for expanding cell culture of the IGF-2 positive cardiac progenitor cells.

Academic Significance and Societal Importance of the Research Achievements

iPS細胞由来心筋細胞の移植治療において、純化成熟心筋細胞への分化誘導、分化抵抗性iPS細胞排除の実現には未だハードルがある。本研究では心筋分化誘導を行ったiPS細胞から心筋分化効率が非常に高いIGF-2陽性心筋前駆細胞を移植細胞として純化・精製することに成功した。iPS細胞由来の心筋前駆細胞の精製・移植による心筋再生を実現する技術は未だに報告がない独創的な試みであり、本研究成果をさらに発展させる事で前駆細胞の特性を生かした幅広い心疾患患者に対する臨床応用への発展が期待できる。