Caveolin-1 Plays an Important Role in the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Cardiomyocytes

Abstract

Objectives: Accumulating evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) may transdifferentiate into cardiomyocytes, making BMSCs a promising source of cardiomyocytes for transplantation. However, little is known about the molecular mechanisms underlying myogenic conversion of BMSCs. Methods: This study was designed to investigate the functional role of caveolin-1 in the cardiomyocyte differentiation of BMSCs and to explore the potential underlying molecular mechanisms. Results: BMSC differentiation was induced by treatment with 10 μ<smlcap>M</smlcap> 5-azacytidine, and immunofluorescence assay showed that the expression of cardiomyocyte marker cardiac troponin T (cTnT) was significantly increased compared with a control group. Meanwhile, an increased caveolin-1 expression was found during the 5-azacytidine-induced BMSC differentiation. Additionally, the role of caveolin-1 in the differentiation process was then studied by using caveolin-1 siRNAs. We found that silencing caveolin-1 during induction remarkably enhanced the expression of cardiomyocyte marker genes, including cTnT, Nkx2.5 (cardiac-specific transcription factor), α-cardiac actin and α-myosin heavy chain (α-MHC). Moreover, we observed that downregulation of caveolin-1 was accompanied by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. Conclusions: Taken together, these findings demonstrate that caveolin-1 plays an important role in the differentiation of BMSCs into cardiomyocytes in conjunction with the STAT3 pathway.

The cardiac niche role in cardiomyocyte differentiation of rat bone marrow-derived stromal cells: comparison between static and microfluidic cell culture methods

“…Recent studies are attempting to discover stem cells with higher potential for the treatment of MI (Ding et al, 2015[6]). The safety and efficiency of BMSCs to treat MI have been shown in animal models (Chen et al, 2017[5]). BMSCs transplantation has demonstrated advantageous results regardless of their possible therapeutic effects; either by differentiation into cardiomyocyte-like cells or acting via paracrine signaling (e.g., by increasing angiogenesis) (He et al, 2010[11]).…”

“…Despite the fact that some kinds of stem cells may be suitable for cell-based therapy in heart failure, bone marrow-derived stromal cells (BMSCs) are appealing since they can be simply extracted and expanded in culture (Antonitsis et al, 2007[1]). It has been shown that BMSC-based therapy and tissue engineering for heart failure is feasible and safe (Chen et al, 2017[5]). In addition, BMSCs were shown to have some other vital biological advantages including angiogenesis, immune modulation, and anti-apoptotic activities (Chen et al, 2017[5]).…”

“…It has been shown that BMSC-based therapy and tissue engineering for heart failure is feasible and safe (Chen et al, 2017[5]). In addition, BMSCs were shown to have some other vital biological advantages including angiogenesis, immune modulation, and anti-apoptotic activities (Chen et al, 2017[5]). Furthermore, the multipotent differentiation of BMSCs endows them with the capability to differentiate into different cell lineages such as chondrocyte, osteocyte and adipocyte-like cells (Chen et al, 2017[5]).…”

Cardiomyocyte differentiation of mesenchymal stem cells from bone marrow: new regulators and its implications

“…Previous reports indicate that Caveolin-1 could play an important role in proliferation and differentiation of BMSCs [ 121 – 123 ], but the role of Caveolin-1 in cardiomyocyte differentiation of BMSCs remains unknown. Chen et al [ 124 ] find that both mRNA and protein levels of Caveolin-1 are increased in 5-aza-treated BMSCs, suggesting that Caveolin-1 may be involved in the differentiation of BMSCs into cardiomyocytes. To further explore the role of Caveolin-1 in BMSC differentiation, Caveolin-1 siRNA is used.…”

Therapeutic effects of conditioned medium from bone marrow-derived mesenchymal stem cells on epithelial-mesenchymal transition in A549 cells

“…Bone marrow-derived mesenchymal stem cells (BMSCs) are pluripotent stem cells derived from bone marrow, with the potential of self-renewal and differentiation into various cell types, such as adipocytes, cardiomyocytes ( 10 ), endotheliocytes and neurons ( 11 ). BMSCs can perceive damage signals and migrate into the damaged area.…”