4.8 Article

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

期刊

JOURNAL OF CONTROLLED RELEASE
卷 336, 期 -, 页码 499-509

出版社

ELSEVIER
DOI: 10.1016/j.jconrel.2021.06.040

关键词

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

资金

  1. National Research Foundation of Korea (NRF) - Korean Government [2015M3A9B4066662]
  2. National Research Foundation of Korea [2015M3A9B4066662] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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Strategies for stem cell-based cardiac regeneration and repair, specifically cardiac stem cells (CSCs) and the use of cellular spheroids, have shown promising therapeutic potential for ischemic heart disease. The optimized spheroid culture conditions enhance the expression levels of factors related to cardiac regeneration, leading to improved retention rates and significant cardiac regeneration effects in animal models. Intramyocardial administration of CSC spheroids could serve as an advanced therapeutic modality for enhanced cell engraftment and regenerative abilities in cardiac repair post-myocardial infarction.
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.

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