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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)77-87
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume174
DOIs
Publication statusPublished - 2023 Jan

Keywords

  • Cardiac spheroid
  • Cell transplantation
  • Intracoronary
  • Myocardial infarction
  • Pluripotent stem cell-derived cardiomyocyte (PSC-CM)
  • cynomolgus monkey

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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