Furthermore, the level of cardiomyogenic differentiation-associated extracellular matrix proteins (collagen I, collagen III, collagen IV, fibronectin, and laminin) in MSCs cultured with graphene supplement is increased. stem cells into osteoblasts, chondrocytes, or adipocytes [95]. The BMP signaling pathway also plays key functions in regulating proliferation, differentiation, and survival of cardiac progenitor cells [96]. The expression of BMP-2 is usually increased after myocardial infarction, not only anti-apoptosis, but also regulating Tmem44 the cardiomyocyte differentiation of cardiac progenitors [97]. By controlling the expression of BMP-2, ES cells could differentiate into cardiomyocytes [98]. A previous study also shows that BMP-2 might differentiate BMSCs into a myocardial cell line. Salvianolic acid B could play a cardioprotective role in ES cell-derived cardiomyocytes in a hypoxia condition. Salvianolic acid B also could regulate the differentiation of various types of cells. For example, Salvianolic acid B promotes osteogenesis of human mesenchymal stem cells [99] and enhances BMSC differentiation into type I alveolar epithelial cells [100]. Salvianolie acid B could be?used to induce myocardial differentiation?of BMSCs due to its function of cardioprotective and regulationg differentiation. Microenvironment Many research studies show that this cell-culture microenvironment may influence cell proliferation and differentiation. Recently, in-vitro studies have shown that culturing cells with specific medium could alter the cardiac-specific gene expression and differentiation of stem cells. Wu et al. [101] utilize a high-voltage electrostatic field system to form nanosized collagen particles from collagen I answer. To further investigate whether collagen E 2012 I nanomolecules could affect BMSC differentiation, BMSCs are cultured in medium with or without collagen I nanoparticles. After 24?h, 5-aza is usually added to induce the cardiomyocyte differentiation of BMSCs. The expression of two transcription factors (GATA4 and Nkx2.5) and four cardiac-specific markers (cTnI, -MHC, CX43, and cardiac -actin) are evaluated in BMSCs pretreatment with collagen I nanomolecules compared with BMSCs which?not exposed to collagen I nanomolecules. These results demonstrate that collagen I nanomolecules can synergize with 5-aza to induce the E 2012 cardiomyocyte differentiation of BMSCs, but the mechanism remains to be further explored. Recently, in-vitro studies have shown that culturing substrates could modulate MSC differentiation [102]. Due to its physical and chemical properties and its effect on differentiation of MSCs [103], graphene has drawn E 2012 much attention as a new type of MSC culture dish. To determine whether graphene could regulate the cardiomyocyte differentiation of human bone marrow-derived MSCs, Park et al. [104] conduct a series of studies. After cell seeding, cardiac-specific markers, including GATA4, cardiac actin, -MHC, and cTnT, are all higher in MSCs cultured on graphene than in MSCs cultured on coverslips. Furthermore, the level of cardiomyogenic differentiation-associated extracellular matrix proteins (collagen I, collagen III, collagen IV, fibronectin, and laminin) in MSCs cultured with graphene supplement is increased. Taken together, these data suggest that graphene could promote cardiomyocyte differentiation of MSCs through differentiation-associated ECM proteins and related signaling pathways. Collagen scaffold has been used as a cell product in clinical trials for cardiac repair [105]. A recent study shows that MSCs could enhance the expression of cardiomyocyte-specific proteins in collagen patches and secrete cardiotrophic factors [106]. Extracellular matrix is an essential property of E 2012 the microenvironment cells interact with, and has a key role in influencing cell behavior and determining cell fate. Furthermore, MSCs cultured in collagen patches provide not only structural support to damaged myocardium but also promote tissue repair and enhance regenerative potential of MSCs [107C109]. Previous studies have shown that stem cellCextracellular matrix (ECM) interactions may take part in the cardiomyogenic differentiation of stem cells [110C112], whereas cardiomyogenic differentiation-associated ECM proteins can induce cardiac differentiation of ES cells [113]. Graphene-based materials have emerged E 2012 with various functions in multiple biomedical applications, such.