Cardioprotective effects of genetically engineered cardiac stem cells by spheroid formation on ischemic cardiomyocytes

Han Saem Jeong, Chi Yeon Park, Jong Ho Kim, Hyung Joon Joo, Seung Cheol Choi, Ji Hyun Choi, I. Rang Lim, Jae Hyoung Park, Soon Jun Hong, Do Sun Lim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Sca-1+ cardiac stem cells and their limited proliferative potential were major limiting factors for use in various studies. Methods: Therefore, the effects of sphere genetically engineered cardiac stem cells (S-GECS) inserted with telomerase reverse transcriptase (TERT) were investigated to examine cardiomyocyte survival under hypoxic conditions. GECS was obtained from hTERT-immortalized Sca-1+ cardiac stem cell (CSC) lines, and S-GECS were generated using poly-HEMA. Results: The optimal conditions for S-GECS was determined to be 1052 GECS cells/mm2 and a 48 h culture period to produce spheroids. Compared to adherent-GECS (A-GECS) and S-GECS showed significantly higher mRNA expression of SDF-1α and CXCR4. S-GECS conditioned medium (CM) significantly reduced the proportion of early and late apoptotic cardiomyoblasts during CoCl2-induced hypoxic injury; however, gene silencing via CXCR4 siRNA deteriorated the protective effects of S-GECS against hypoxic injury. As downstream pathways of SDF-1α/CXCR4, the Erk and Akt signaling pathways were stimulated in the presence of S-GECS CM. S-GECS transplantation into a rat acute myocardial infarction model improved cardiac function and reduced the fibrotic area. These cardioprotective effects were confirmed to be related with the SDF-1α/CXCR4 pathway. Conclusions: Our findings suggest that paracrine factors secreted from transplanted cells may protect host cardiomyoblasts in the infarcted myocardium, contributing to beneficial left ventricle (LV) remodeling after acute myocardial infarction (AMI).

Original languageEnglish
Article number15
JournalMolecular Medicine
Volume26
Issue number1
DOIs
Publication statusPublished - 2020 Jan 31

Keywords

  • CXCR4
  • Cardiac sphere, acute myocardial infarction
  • Cardioprotection
  • SDF-1α
  • Sca-1+ cardiac stem cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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