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

Mater Sci Eng C Mater Biol Appl. 2018 Dec 1:93:61-69. doi: 10.1016/j.msec.2018.07.061. Epub 2018 Jul 24.

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.

Keywords: Differentiation; Extracellular matrix; Fibroblasts; Growth factors cocktail; Mesenchymal stem cells; Smooth muscle cells.

MeSH terms

  • Blood Vessel Prosthesis*
  • Cell Differentiation*
  • Coculture Techniques
  • Extracellular Matrix / chemistry*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Tissue Engineering*