Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration

Hideki Kobayashi, Shugo Tohyama, Hideaki Kanazawa, Hajime Ichimura, Shuji Chino, Yuki Tanaka, Yota Suzuki, Jian Zhao, Naoko Shiba, Shin Kadota, Kazumasa Narita, Takafumi Naito, Tatsuichiro Seto, Koichiro Kuwahara, Yuji Shiba, Keiichi Fukuda

研究成果: ジャーナルへの寄稿学術論文査読

10 被引用数 (Scopus)

抄録

Advances in stem cell biology have facilitated cardiac regeneration, and many animal studies and several initial clinical trials have been conducted using human pluripotent stem cell-derived cardiomyocytes (PSC-CMs). Most preclinical and clinical studies have typically transplanted PSC-CMs via the following two distinct approaches: direct intramyocardial injection or epicardial delivery of engineered heart tissue. Both approaches present common disadvantages, including a mandatory thoracotomy and poor engraftment. Furthermore, a standard transplantation approach has yet to be established. In this study, we tested the feasibility of performing intracoronary administration of PSC-CMs based on a commonly used method of transplanting somatic stem cells. Six male cynomolgus monkeys underwent intracoronary administration of dispersed human PSC-CMs or PSC-CM aggregates, which are called cardiac spheroids, with multiple cell dosages. The recipient animals were sacrificed at 4 weeks post-transplantation for histological analysis. Intracoronary administration of dispersed human PSC-CMs in the cynomolgus monkeys did not lead to coronary embolism or graft survival. Although the transplanted cardiac spheroids became partially engrafted, they also induced scar formation due to cardiac ischemic injury. Cardiac engraftment and scar formation were reasonably consistent with the spheroid size or cell dosage. These findings indicate that intracoronary transplantation of PSC-CMs is an inefficient therapeutic approach.

本文言語英語
ページ(範囲)77-87
ページ数11
ジャーナルJournal of Molecular and Cellular Cardiology
174
DOI
出版ステータス出版済み - 01-2023
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 循環器および心血管医学

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