Vascular extracellular matrix and fibroblasts-coculture directed differentiation of human mesenchymal stem cells toward smooth muscle-like cells for vascular tissue engineering

Abstract

Construction of an artificial vascular graft is widely considered a promising strategy in vascular tissue engineering. However, limited sources of functional vascular smooth muscle cells (VSMCs) remain a major obstacle in vascular tissue engineering. In this study, we innovatively developed an approach to obtain functional VSMCs by onsite differentiating human bone marrow-derived mesenchymal stem cells (MSCs) directed by decellularized extracellular matrix (ECM) and fibroblasts. The resulting cells and ECM-cells constructs were characterized by real time RT-PCR, immunofluorescence staining, cell contractile functions, and migration capacity. Our results showed both ECM and fibroblasts induced MSCs differentiation toward VSMC-like cells with increased transcription of marker genes, upregulated expression of contractile apparatus proteins, and enhanced functional activity of VSMC phenotype. Interestingly, our findings revealed that native ECM and fibroblasts-coculture had a higher potential to promote MSCs differentiation into VSMCs than growth factors cocktail (GFC) supplemented culture, thereby providing a potential source of VSMCs for blood vessel constitution.