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Published on: May 25, 2020
[Anti-apoptotic effects of mesenchymal stem cells on cardiac myocytes: in vitro study with rats]
Huan Qu1, Yan-hong Guo, Xiao-jun Zhu
1Department of Cardiology, Peking University Third Hospital, Institute of Cardiovascular Research, Peking University Health Sciences Center, Beijing 100083, China.
Objective:
To investigate the anti-apoptotic effects of mesenchymal stem cells (MSCs) on hypoxia-injured cardiac myocytes.
Methods:
MSCs were isolated from the bone marrow of 6 - 8 week-old Sprague-Dawley rats. Cardiac myocytes from neonatal rat were cultured under hypoxia, then the hypoxia-injured cardiac myocytes were divided into 3 groups: cultured alone (control group), co-cultured with the MSCs, or co-cultured in MSC-conditioned media in conditions of anoxia (95% N(2) + 5% CO(2), continuous hypoxia group) or normoxia [hypoxia/reoxygen (H/R) group] for 72 hours. The cell apoptosis was measured by Hoechst staining, and Western blotting was used to test the protein expression of Bcl-2 and Bax in the cardiac myocytes.
Results:
The apoptotic rate of the cardiac myocytes cultured under hypoxia was 51.6% +/- 2.4%, significantly higher than those of the cardiac myocytes co-cultured with MSCs and MSC-conditioned media respectively (15.1% +/- 5.4% and 24.0% +/- 4.2% respectively, both P < 0.001). The apoptotic rate of the H/R group was 20.9% +/- 2.7%, significant higher than that of the MSC group (11.5% +/- 3.7%, P < 0.05), however, not significantly different from that of the MSC-conditioned media group (20.1% +/- 4.2%, P > 0.05). The protein expression of Bcl-2 was not significantly different among different groups. The Bax protein expression of the MSC group and MSC-conditioned media group were 2.28 +/- 0.46 and 3.01 +/- 0.26 respectively, both significantly lower than that of the control group (7.62 +/- 1.28, both P < 0.05). The decreased expression of Bax in the cardiac myocytes was greatly related to the decreasing of apoptosis.
Conclusion:
Co-cultured MSCs show significant anti-apoptotic effects on cardiac myocytes both in continuous hypoxia and in H/R conditions with the possible mechanism of direct cell to cell interaction and paracrine of cytokines which effect the expression of Bax in the myocytes.
Insights
Mesenchymal stem cells (MSCs) significantly reduce apoptosis in cardiac myocytes damaged by hypoxia. This protective effect is mediated by MSCs directly interacting with cells or through secreted factors influencing Bax protein expression.
Area of Science:
- Cardiology
- Stem Cell Biology
- Cellular Biology
Background:
- Hypoxia-induced cardiac myocyte apoptosis is a key factor in heart damage.
- Mesenchymal stem cells (MSCs) are being investigated for their therapeutic potential in cardiovascular diseases.
Purpose of the Study:
- To evaluate the anti-apoptotic effects of MSCs on cardiac myocytes subjected to hypoxic injury.
- To explore the underlying mechanisms of MSC-mediated cardioprotection.
Main Methods:
- MSCs were isolated from rat bone marrow.
- Cardiac myocytes were cultured under hypoxic conditions and treated with MSCs or MSC-conditioned media.
- Apoptosis was assessed using Hoechst staining.
- Protein expression of Bcl-2 and Bax was analyzed via Western blotting.
Main Results:
- MSCs and MSC-conditioned media significantly reduced cardiac myocyte apoptosis under both continuous hypoxia and hypoxia/reoxygenation (H/R) conditions.
- MSC treatment led to a significant decrease in Bax protein expression, correlating with reduced apoptosis.
- Bcl-2 expression remained unchanged across groups.
Conclusions:
- MSCs exert significant anti-apoptotic effects on cardiac myocytes under hypoxic stress.
- Cardioprotection may involve direct cell-cell contact and paracrine signaling, modulating Bax expression.
- These findings highlight MSCs as a potential therapeutic strategy for myocardial injury.

