微小心筋組織作製の最適条件を決定し、酸素供給の重要性および成熟度を確認した。良質な心筋細胞獲得のためにヒトiPS細胞由来心筋細胞の二次元大量培養法を確立した。免疫不全マウスの心臓に移植された心筋組織は長期移植後も大量に生着し血管構築が確認された。また、心筋梗塞モデルの免疫不全ラットに移植された心筋組織は長期移植後も大量に生着し、心機能が有意に改善することを確認した。生着した心筋組織はconnexin43を発現し、有意な致死性不整脈は全く確認されなかった。これらの成果より、高純度なヒト心筋細胞を基盤とした移植微小心筋組織は血管構築を有し、安全かつ効率よく心機能を改善させることが明らかになった。
The optimal conditions for preparation of micro-cardiac tissues (MCT) were determined. Their maturity and the importance of the oxygen supply were confirmed. We established a massive two-dimensional culture method of human iPS cell-derived cardiomyocytes to obtain high-quality cardiomyocytes. MCT were transplanted to hearts of immunodeficient mice. The transplanted MCT were engrafted in large quantities even in the long term after transplantation, and vascular network was confirmed. MCT was transplanted to myocardial infarction models in immunodeficient rats, as well. A large number of transplanted MCT were engrafted, and their cardiac function significantly improved even in the long term after transplantation. The engrafted MCT expressed connexin 43 and did not induce any lethal arrhythmia. From these results, it has become clear that MCT based on high-quality human cardiomyocytes has vascular network, and safely and efficiently improves cardiac function in heart failure.

研究種目 : 基盤研究 (C) (一般)
研究期間 : 2016～2018
課題番号 : 16K09507
研究分野 : 循環器内科