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

血管细胞外基质和成纤维细胞共培养定向人类间充质干细胞向平滑肌样细胞分化用于血管组织工程

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作者:Na Li, Hanna Sanyour, Tyler Remund, Patrick Kelly, Zhongkui Hong

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.

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