Cyclic mechanical strain promotes transforming‐growth‐factor‐β1‐mediated cardiomyogenic marker expression in bone‐marrow‐derived mesenchymal stem cells in vitro

Abstract

Cardiomyocytes in the heart reside in mechanically dynamic environments, such as those subject to cyclic mechanical strain. TGF-beta1 (transforming growth factor-beta1) stimulates cardiomyogenic marker expression of BMMSCs (bone-marrow-derived mesenchymal stem cells). In the present study, we tested the hypothesis that cyclic mechanical strain promotes TGF-beta1-mediated cardiomyogenic marker expression in BMMSCs in vitro. The mRNA expression of cardiac-specific genes was more up-regulated in BMMSCs cultured with a TGF-beta1 supplement and subjected to cyclic strain for 1 week than in BMMSCs cultured statically with a TGF-beta1 supplement. Immunocytochemical analyses and flow cytometric analysis showed that the proportions of cardiac troponin-I-positive cells and cardiac MHC (myosin heavy chain)-positive cells and the proportions of cells expressing tropomyosin respectively were increased to a greater extent by TGF-beta1with cyclic strain than by TGF-beta1 alone. These results showed that cyclic strain promotes TGF-beta1mediated cardiomyogenic marker expression in BMMSCs in vitro.

TGF-β1 induces apoptosis of bone marrow-derived mesenchymal stem cells via regulation of mitochondrial reactive oxygen species production

“…Generally, BMSCs must be induced in vitro for directional differentiation prior to transplantation. TGF-β1 is one of the most commonly used reagents to induce the directional differentiation of BMSCs into cardiomyocyte-like cells (6)(7)(8). In the present study, it was found that the viability of the BMSCs was markedly decreased and the apoptosis rates of the BMSCs were increased following exposure to 10 and 20 ng/ml TGF-β1 for 24 h. Furthermore, the mitochondrial ROS levels were notably increased in the TGF-β1-treated BMSCs.…”

“…TGF-β1 was the first-identified isoform in the TGF-β family, and is the most important isoform in the regulation of cell growth and differentiation (29). A number of studies have used TGF-β1 to induce the cardiomyogenic differentiation of BMSCs and have successfully acquired cardiomyocyte-like cells using this method (6)(7)(8); however, several lines of evidence suggest that TGF-β1 acts to trigger apoptosis of numerous cell types (15)(16)(17). In the present study, it was found that TGF-β1 inhibited the proliferation and promoted the apoptosis of BMSCs.…”

“…Generally, BMSCs need to be induced in vitro by special reagents for cardiomyogenic differentiation. Transforming growth factor-β1 (TGF-β1) is one of the most commonly used reagents for inducing the cardiomyogenic differentiation of BMSCs (6)(7)(8). Previous studies have indicated that TGF-β1 treatment in vitro promotes the transformation of BMSCs into cardiomyocyte-like cells that express cardiomyocyte-specific markers (6)(7)(8).…”

Modulation of Stem Cell Differentiation with Biomaterials

“…Either cyclic strain (25) or TGF-β1 (27) alone can stimulate the cardiomyogenic differentiation of stem cells. A study has shown that combination of TGF-β1 supplementation and cyclic strain application upregulated the expression of cardiac-specific markers in MSCs than TGF-β1 supplementation alone (28). The combination of cyclic strain and TGF-β1 induced the expression of troponin-I or cardiac myosin heavy chain in an average of 44.5% of treated MSCs (28).…”

“…A study has shown that combination of TGF-β1 supplementation and cyclic strain application upregulated the expression of cardiac-specific markers in MSCs than TGF-β1 supplementation alone (28). The combination of cyclic strain and TGF-β1 induced the expression of troponin-I or cardiac myosin heavy chain in an average of 44.5% of treated MSCs (28). Previous studies reported that cardiomyogenic differentiation of MSCs can be achieved by co-culturing with rat cardiomyocytes (29,30) or treatment with 5-azacytidine (31).…”