ONO-1301 enhances post-transplantation survival of human induced pluripotent stem cell-derived cardiac tissue sheet by promoting angiogenesis

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
出处
期刊:Journal of Heart and Lung Transplantation [Elsevier]
卷期号:42 (6): 716-729 被引量:6
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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