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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
In vitro and in vivo effects of bone marrow stem cells on cardiac structure and function
Meifeng Xu1, Ryota Uemura, Ying Dai
1Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
Insights
Bone marrow stem cells (BMSCs) protect the heart by releasing factors that prevent cardiac cell death and improve function after myocardial infarction. This paracrine effect aids in early cardiac repair.
Area of Science:
- Cardiovascular biology
- Regenerative medicine
- Stem cell research
Background:
- Bone marrow stem cells (BMSCs) show potential in protecting ischemic myocardium.
- Protection may involve anti-apoptotic effects mediated by paracrine mechanisms.
Purpose of the Study:
- To investigate the protective role of BMSCs on ischemic myocardium.
- To identify paracrine factors secreted by BMSCs and their effect on cardiomyocyte apoptosis and cardiac function.
Main Methods:
- Detection of cytokines (VEGF, bFGF, SDF-1, IGF-1) in BMSC culture medium using ELISA.
- Assessment of myocyte apoptosis via DNA fragmentation and annexin-V staining.
- Induction of myocardial infarction in mice, followed by stem cell factor (SCF) treatment and analysis of cardiac function, apoptosis, and Bcl-2 expression.
Main Results:
- BMSCs secreted VEGF, bFGF, SDF-1, and IGF-1.
- Co-culture with BMSCs reduced hypoxia-induced cardiomyocyte apoptosis.
- SCF treatment improved cardiac function, reduced apoptosis, and increased Bcl-2 expression in the ischemic area.
- BMSC-conditioned medium upregulated Bcl-2 protein in cardiomyocytes.
Conclusions:
- Paracrine mediators from BMSCs are involved in the early repair of ischemic heart.
- These mediators prevent cardiomyocyte apoptosis and improve cardiac function.
- BMSCs offer a potential therapeutic strategy for myocardial infarction.
Abstract:
It is hypothesized that the protection of bone marrow stem cells (BMSCs) on ischemic myocardium might be related to the anti-apoptotic effect via paracrine mechanisms. In this study, a wide array of cytokines including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), stromal cell-derived factor-1 (SDF-1) and insulin growth factor-1 (IGF-1) were detected in the BMSCs cultured medium by ELISA. Myocyte apoptosis was assayed by DNA fragmentation and annexin-V staining. Myocardial infarction model was produced by ligation of mouse left anterior descending coronary artery (LAD). Before LAD ligation, mice were myoablated by irradiation and transplanted with bone marrow cells from transgenic mice expressing green fluorescent protein (GFP). After LAD ligation, animals were administered stem cell factor (SCF, 200 mug/day/kg, i.p.) or saline for 6 days. Animals were sacrificed at 4 weeks after SCF treatment. Apoptotic cardiomyocytes were analyzed by TUNEL. Myocardial function was analyzed by echocardiography and pressure-volume system. Bcl-2 protein was analyzed by Western blotting. Our results showed that cultured BMSCs released VEGF, bFGF, SDF-1 and IGF-1. Hypoxia-induced cell apoptosis was diminished in cardiomyocytes co-cultured with BMSCs. Smaller LV dimension and increased LV ejection fraction were seen in SCF-treated animals. SCF significantly reduced cardiomyocytes apoptosis within peri-infarct area and increased up-regulation expression of Bcl-2 in ischemic area. Moreover, conditioned medium from cultured BMSCs also induced up-regulation of Bcl-2 protein in cardiomyocytes. It is concluded that paracrine mediators secreted by BMSCs might be involved in early repair of ischemic heart by preventing cardiomyocytes apoptosis and improving cardiac function.

