Effects of Human Fibroblast-Derived Extracellular Matrix on Mesenchymal Stem Cells

Stem cell fate is largely determined by the microenvironment called niche. The extracellular matrix (ECM), as a key component in the niche, is responsible for maintaining structural stability and regulating cell proliferation, differentiation, migration and other cellular activities. Each tissue has a unique ECM composition for its needs. Here we investigated the effect of a bioengineered human dermal fibroblast-derived ECM (hECM) on the regulation of human mesenchymal stem cell (hMSC) proliferation and multilineage differentiation. Human MSCs were maintained on hECM for two passages followed by the analysis of mRNA expression levels of potency- and lineage-specific markers to determine the capacity of MSC stemness and differentiation, respectively. Mesenchymal stem cells pre-cultured with or without hECM were then induced and analyzed for osteogenesis, adipogenesis and chondrogenesis. Our results showed that compared to MSCs maintained on control culture plates without hECM coating, cells on hECM-coated plates proliferated more rapidly with a higher percentage of cells in S phase of the cell cycle, resulting in an increase in the CD90⁺/CD105⁺/CD73⁺/CD45^- subpopulation. In addition, hECM downregulated osteogenesis and adipogenesis of hMSCs but significantly upregulated chondrogenesis with increased production of collagen type 2. In sum, our findings suggest that hECM may be used to culture hMSCs for the application of cartilage tissue engineering.