血管生成
移植
医学
治疗性血管生成
新生血管
内科学
心脏病学
生物
作者
Xiang Qu,Junjun Li,Li Liu,Jingbo Zhang,Ying Hua,Kota Suzuki,Akima Harada,Masako Ishida,Noriko Yoshida,Daisuke Okuzaki,Yoshiki Sakai,Yoshiki Sawa,Shigeru Miyagawa
标识
DOI:10.1016/j.healun.2023.01.018
摘要
Transplanting human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) tissue sheets effectively treat ischemic cardiomyopathy. Cardiac functional recovery relies on graft survival in which angiogenesis played an important part. ONO-1301 is a synthetic prostacyclin analog with proangiogenic effects. We hypothesized that transplantation of hiPSC-CM tissue sheets with slow-release ONO-1301 scaffold could promote hostgraft angiogenesis, enhance tissue survival and therapeutic effect. We developed hiPSC-CM tissue sheets with ONO-1301 slow-release scaffold and evaluated their morphology, gene expression, and effects on angiogenesis. Three tissue sheet layers were transplanted into a rat myocardial infarction (MI) model. Left ventricular ejection fraction, gene expression in the MI border zone, and angiogenesis effects were investigated 4 weeks after transplantation. In vitro assessment confirmed the slow-release of ONO-1301, and its pro-angiogenesis effects. In addition, in vivo data demonstrated that ONO-1301 administration positively correlated with graft survival. Cardiac tissue as thick as ∼900 μm was retained in the ONO (+) treated group. Additionally, left ventricular ejection fraction of the ONO (+) group was significantly enhanced, compared to ONO (−) group. The ONO (+) group also showed significantly improved interstitial fibrosis, higher capillary density, increased number of mature blood vessels, along with an enhanced supply of oxygen, and nutrients. Slow-release ONO-1301 scaffold provided an efficient delivery method for thick hiPSC-CM tissue. ONO-1301 promotes angiogenesis between the host and graft and improves nutritional and oxygen supply, thereby enhancing the survival of transplanted cells, effectively improving ejection fraction, and therapeutic effects.
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