Abstract 19996: Cardiac Mesenchymal Stem Cells With High Endogenous Gata4 Promoter Activity Have Superior Capacity to Elicit Cardiac Repair
Introduction: Given the limited success to date in using non-specific membrane makers, in identifying cardiac stem cells, the significance of finding a much more potential cardiac mesenchymal stem cell (C-MSC) maker from transcription factors in nuclear is very important.
Hypothesis: We want to test the feasibility of using GATA4, an early cardiac-specific transcription factor, as biomarker to identify a subpopulation of C-MSC that could be highly efficacious for cardiovascular repair.
Methods: A lentiviral vector in which the expression of eGFP reporter is driven by a 1kb fragment of the mouse GATA4 promoter was constructed. Murine C-MSC with high GFP intensity were sorted by FACS.
Results: Western blot shows that the C-MSC population with high GFP intensity exhibits higher GATA4 protein expression as compared with unsorted C-MSC. Interestingly, we observed that sorted GATA4high C-MSC also exhibit higher HIF-1α protein expression as compared with unsorted C-MSC. We compared hypoxia- and serum deprivation induced-apoptosis between sorted GATA4high and unsorted C-MSC by TUNEL staining. We found that the GATA4high exhibited lower rate of TUNEL positivity as compared with unsorted C-MSC, suggesting GATA4high C-MSC are more resistant to hypoxia- and serum deprivation-induced apoptosis in comparison with unsorted C-MSC. In mouse model of myocardial infarction by permanent left coronary ligation, GATA4high C-MSC or unsorted C-MSC was injected into the border zone area. Left ventricular ejection fraction (EF) were serially (days 1 and 14) assessed using echocardiography. At day 1, no differences in EF were observed between GATA4high C-MSC and unsorted C-MSC group (n=9, ns). At day 14, left ventricular ejection fraction in GATA4high C-MSC cell-treated group was improved about 11.2% compared with the unsorted C-MSC group (n=9, P<0.05).
Conclusions: Our results suggest that GATA4high, as compared with unsorted C-MSC, exhibit enhanced survival capacity which will consequently lead to improvement of heart contractile function in the infarcted heart, therefore, GATA4high C-MSC can be considered as a much more potential progenitor for heart repair.
Author Disclosures: Y. Wang: None. J. Rubinstein: None. X. Wang: None. I. Kim: None. M. Ashraf: None. N. Weintraub: None. Y. Tang: None.
- © 2016 by American Heart Association, Inc.