Intramyocardial delivery of human cardiac stem cell spheroids with enhanced cell engraftment ability and cardiomyogenic potential for myocardial infarct repair

Min Ah Han, Jeong Hwa Jeon, Ji Young Shin, Hee Jung Kim, Ji Soo Lee, Chae Won Seo, Ye Jin Yun, Mi Yun Yoon, Jong Tae Kim, Young Il Yang, Seung Jin Lee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Strategies for stem cell-based cardiac regeneration and repair are key issues for the ischemic heart disease (IHD) patients with chronic complications related to ischemic necrosis. Cardiac stem cells (CSCs) have demonstrated high therapeutic efficacy for IHD treatment owing to their specific cardiac-lineage commitment. The therapeutic potential of CSCs could be further enhanced by designing a cellular spheroid formulation. The spheroid culture condition of CSCs was optimized to ensure regulated size and minimal core necrosis in the spheroids. The CSC spheroids revealed mRNA profiles of the factors related to cardiac regeneration, angiogenesis, anti-inflammatory, and cardiomyocyte differentiation with a higher expression level than the CSCs. Intramyocardially delivered CSC spheroids in the rat IHD model resulted in a significant increase in retention rate by 1.82-fold (day 3) and 1.98-fold (day 14) compared to CSCs. Endothelial cell differentiation and neovascularization of the engrafted CSC spheroids were noted in the infarcted myocardium. CSC spheroids significantly promoted cardiac regeneration: i.e., decreased infarction and fibrotic area (11.22% and 4.18%) and increased left ventricle thickness (0.62 mm) compared to the untreated group. Cardiac performance was also improved by 2.04-fold and 1.44-fold increase in the ejection fraction and fractional shortening, respectively. Intramyocardial administration of CSC spheroids might serve as an advanced therapeutic modality with enhanced cell engraftment and regenerative abilities for cardiac repair after myocardial infarction.

Original languageEnglish
Pages (from-to)499-509
Number of pages11
JournalJournal of Controlled Release
Volume336
DOIs
StatePublished - 10 Aug 2021

Keywords

  • Cardiac regeneration
  • Human cardiac stem cell
  • Intramyocardial delivery
  • Ischemic heart disease
  • Spheroid culture

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