Protective paracrine effect of mesenchymal stem cells on cardiomyocytes

Abstract

Abstract:Objective: The aim of this study was to test the protective effect of mesenchymal stem cells (MSCs) on cardiomyocytes in vitro and to investigate the anti-apoptotic signaling pathway. Methods: MSCs from Sprague-Dawley (SD) rats were separated and cultured. MSC medium was collected from MSCs cultured in serum-free Dulbecco's modified eagle medium (DMEM) under hypoxia. Cultured cardiomyocytes from neonatal SD rats were exposed to hypoxia/reoxygenation (H/R) and treated with MSC medium. The apoptotic cardiomyocytes were stained with Annexin-V-fluorescein isothiocyanate (FITC), Hoechst 33342 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). The mitochondrial transmembrane potential of cardiomyocytes was assessed using a fluorescence microscope. The expression of Bcl-2, Bax, cytochrome C, apoptosis-induced factor (AIF), and caspase-3 was tested by Western blot analysis. Results: Our data demonstrated that MSC medium reduced H/R-induced cardiomyocyte apoptosis, increased the Bcl-2/Bax ratio, and reduced the release of cytochrome C and AIF from mitochondria into the cytosol. Conclusion: MSCs protected the cardiomyocytes from H/R-induced apoptosis through a mitochondrial pathway in a paracrine manner.

Reconstitute the damaged heart via the dual reparative roles of pericardial adipose-derived flk-1+ stem cells

“…5A has demonstrated that many cardiomyocytes within the newly formed myocardium were mitotically incorporated with BrdU, suggesting that the newly formed cardiomyocytes are ensured. Therefore, the beneficial structural sequelae by flk-1 pos pADSC are associated with neoangiogenesis in particular of microvasculature and myogenic formation of bone fide cardiac cells, rather than the anti-apoptotic or cardiac protective effects that have been proposed by others [27].…”

Upregulation of heme oxygenase-1 expression by hydroxysafflor yellow A conferring protection from anoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes

“…Caspase-3 is one of the most pivotal effector caspases that is sequentially activated, autocatalyzed, and processed into activated fragments during apoptosis [31]. Level of cleaved caspase-3, the activated fragment, is regarded as an index of apoptosis intensity [32]. The results of flow cytometric detection indicated that HSYA reduced the apoptosis rate of the H9c2 cardiomyocytes subjected to A/R, and this anti-apoptotic state was notably blocked by ZnPP-IX.…”

Effects of insulin-like growth factor-1 on the properties of mesenchymal stem cells in vitro

“…While the clinical data are encouraging (Chen et al, 2004;Katritsis et al, 2005), controversies regarding the mechanisms responsible for the cardioprotective effects of MSCs remain. It was hypothesized that the paracrine effect of MSCs plays an important role in protecting cardiomyocytes and improving cardiac function post transplantation (Tang et al, 2005;Xu et al, 2007;Xiang et al, 2009). Insulin-like growth factor-1 (IGF-1) is one of the key cytokines secreted by MSCs post transplantation (Nagaya et al, 2005;Xu et al, 2007;Tao et al, 2010).…”