Nano‐sized collagen I molecules enhanced the differentiation of rat mesenchymal stem cells into cardiomyocytes

Abstract

The aim of this study was to investigate the ability of nano-sized collagen I molecules (nanoparticles or nanofibrils) and a 5-azacytidine (5-aza) treatment to enhance the differentiation of rat mesenchymal stem cells (MSCs) toward a cardiomyogenic phenotype in vitro. Second passaged MSCs were cocultured with nano-sized collagen I molecules for 24 h and then treated with 10 μM 5-aza for 24 h. The results demonstrated that the size of the cells increased significantly and acquired a flattened, triangular-shaped morphology after treatment with nano-sized collagen I molecules and 5-aza. The cells are connecting with adjoining cells by forming myotube-like structures. Additional treatment of the MSCs with nano-sized collagen I fibrils significantly increased two transcription factors GATA-4 (12.6-fold increase) and Nkx2.5 (4.8-fold increase) expressions compared with MSC groups treated only with 5-aza at 3-day culturing. Furthermore, MSCs pretreated with nano-sized collagen fibrils significantly increased the expressions of cardiac genes of troponin I, β-myosin heavy chain, and cardiac α-actin compared with MSC groups treated only with 5-aza (all, p < 0.01 or better). These results indicate that culturing MSCs with nano-sized collagen I molecules, which may act as scaffolds or soluble protein ingredients, leads to alterations in gene expression and affects the differentiation fate induced with 5-aza.

Functional comparison of beating cardiomyocytes differentiated from umbilical cord‐derived mesenchymal/stromal stem cells and human foreskin‐derived induced pluripotent stem cells

“…showed myotube-like morphology as compared to nontreated control cells (Figure 10e). Nonbeating of troponin T and sarcomeric α-actin positive CMs, differentiated from MSCs, has also been reported earlier by several authors(Kang et al, 2013;Safaeijavan et al, 2014) Safaeijavan et al (2014). The cells were connected with adjacent cells and become multinucleated (Figure 10h).…”

Enhancement of human mesenchymal stem cell differentiation by combination treatment with 5-azacytidine and trichostatin A

“…An approach that involves functional modification of MSCs, such as gene overexpression, three dimensional culture system, immunomodulation, inhibition of apoptosis, stimulation of regeneration, and epigenetic modulation of MSCs could be an attractive way to control MSC differentiation (Hsiao et al 2010). In other studies using HMA, skeletal myogenesis of mouse dental stem cells and cardiomyogenesis of MSCs were enhanced by 5-aza-2 0 -deoxycytidine or its combination with collagen I nanomolecules (Kang et al 2013). In other studies using HMA, skeletal myogenesis of mouse dental stem cells and cardiomyogenesis of MSCs were enhanced by 5-aza-2 0 -deoxycytidine or its combination with collagen I nanomolecules (Kang et al 2013).…”

Cardiomyogenic differentiation of human bone marrow‐derived mesenchymal stem cell spheroids within electrospun collagen nanofiber mats

“…On the other hand, the expressions of connexin‐43 and sarcomeric α‐actin in differentiated cells improved with aza‐treatment in day 28 cultures. In similar studies, when rat MSCs were induced differentiation with exogenous delivery of 10 μM aza and type I collagen nanofibrils, they expressed higher GATA4 and Nkx 2.5 gene expressions on day 3 compared to day 6, and in cultures treated only with 10 μM aza on day 3 or 6 . MSCs exposed to aza and cultured on collagen nanofibrils showed higher cTnI and MHC gene‐expressions by day 6, compared to day 3 cultures or in cells treated only with aza on days 3 or 6 .…”