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- Title
Cardioprotective effects of genetically engineered cardiac stem cells by spheroid formation on ischemic cardiomyocytes.
- Authors
Jeong, Han Saem; Park, Chi-Yeon; Kim, Jong-Ho; Joo, Hyung Joon; Choi, Seung-Cheol; Choi, Ji-Hyun; Lim, I-Rang; Park, Jae Hyoung; Hong, Soon Jun; Lim, Do-Sun
- 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).
- Subjects
STEM cells; TELOMERASE reverse transcriptase; MYOCARDIAL infarction; HEART cells; GENE silencing
- Publication
Molecular Medicine, 2020, Vol 26, Issue 1, p1
- ISSN
1076-1551
- Publication type
Article
- DOI
10.1186/s10020-019-0128-8