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Published on: January 7, 2019
The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling
Xiaohong Wang1, Qingsong Hu, Yasuhiro Nakamura
1Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, 55455, USA. wangx270@umn.edu
Insights
Cardiac stem cell-like Sca-1(+)/CD31(-) cells promote heart repair after myocardial infarction. These cells improve cardiac function and reduce adverse remodeling through paracrine signaling, offering therapeutic potential for ischemic heart disease.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Stem Cell Biology
Background:
- Adult hearts contain cardiac stem cell-like populations whose roles in repair are unclear.
- Sca-1 is a key surface marker for cardiac and somatic stem cells.
- Myocardial infarction (MI) triggers cardiac remodeling and functional decline.
Purpose of the Study:
- To investigate the role of heart-derived Sca-1(+)/CD31(-) cells in myocardial infarction-induced cardiac repair.
- To determine if these cells can differentiate into endothelial and cardiomyocyte lineages.
- To assess the therapeutic potential of Sca-1(+)/CD31(-) cell transplantation in a mouse model of MI.
Main Methods:
- Isolation and in vitro culture of mouse heart-derived Sca-1(+)/CD31(-) cells.
- Induction of myocardial infarction in mice.
- Transplantation of Sca-1(+)/CD31(-) cells into infarcted hearts.
- Assessment of cardiac function (ejection fraction, dimensions) and structure (remodeling, neovascularization, cardiomyocyte regeneration) using immunofluorescence, FACS, and Western blotting.
- Evaluation of myocardial bioenergetic characteristics.
Main Results:
- In vitro cultured Sca-1(+)/CD31(-) cells expressed endothelial and cardiomyocyte markers.
- Endogenous Sca-1(+)/CD31(-) cells and Sca-1 protein expression increased in mouse hearts 7 days post-MI.
- Transplantation of Sca-1(+)/CD31(-) cells improved left ventricular ejection fraction and reduced adverse remodeling.
- Cell therapy significantly increased myocardial neovascularization and promoted modest cardiomyocyte regeneration.
- Improved cardiac function was associated with enhanced myocardial bioenergetics.
Conclusions:
- Heart-derived Sca-1(+)/CD31(-) cells possess stem cell-like properties and contribute to cardiac repair post-MI.
- Transplanted Sca-1(+)/CD31(-) cells exert beneficial effects primarily through paracrine mechanisms, promoting neovascularization and native cardiomyocyte function.
- Sca-1(+)/CD31(-) cells represent a promising therapeutic target for treating ischemic heart disease.
Abstract:
Cardiac stem cell-like populations exist in adult hearts, and their roles in cardiac repair remain to be defined. Sca-1 is an important surface marker for cardiac and other somatic stem cells. We hypothesized that heart-derived Sca-1(+)/CD31(-) cells may play a role in myocardial infarction-induced cardiac repair/remodeling. Mouse heart-derived Sca-1(+)/CD31(-) cells cultured in vitro could be induced to express both endothelial cell and cardiomyocyte markers. Immunofluorescence staining and fluorescence-activated cell sorting analysis indicated that endogenous Sca-1(+)/CD31(-) cells were significantly increased in the mouse heart 7 days after myocardial infarction (MI). Western blotting confirmed elevated Sca-1 protein expression in myocardium 7 days after MI. Transplantation of Sca-1(+)/CD31(-) cells into the acutely infarcted mouse heart attenuated the functional decline and adverse structural remodeling initiated by MI as evidenced by an increased left ventricular (LV) ejection fraction, a decreased LV end-diastolic dimension, a decreased LV end-systolic dimension, a significant increase of myocardial neovascularization, and modest cardiomyocyte regeneration. Attenuation of LV remodeling was accompanied by remarkably improved myocardial bioenergetic characteristics. The beneficial effects of cell transplantation appear to primarily depend on paracrine effects of the transplanted cells on new vessel formation and native cardiomyocyte function. Sca-1(+)/CD31(-) cells may hold therapeutic possibilities with regard to the treatment of ischemic heart disease.
