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

Abstract

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.

Microgrooved-surface topography enhances cellular division and proliferation of mouse bone marrow-derived mesenchymal stem cells

“…On the contrary, histological staining of MMSCs-differentiated pellet showed higer compactness and secretion of several key components of ECM such as collagen II and chondroitin sulflate, resulting into significantly better chondrogenic differentiation compared to MSCs ( Fig 6E & 6F ). These findings, with regard to differentiation potential of MSCs and MMSCs, are quite comparable with published reports [ 23 , 27 , 29 , 37 ].…”

“…This finding clearly establishes positive association between level of their expression and cell proliferation. Therefore, MMSCs showing significantly enhanced basal expression of pluripotency-associated markers such as Nanog, Sox2 and Myc and Oct3/4, compared to BMCs and MSCs ( Fig 7A & 7B ), may be implicated for higher percentage of MMSCs in S/G2-M phases across various passages, and consequently enhanced cellular proliferation as found in our experiment ( Fig 8A & 8B ), as well as observed in similar conditions by recently published reports [ 29 , 33 ].…”

“…In this study, we investigated effects of microgrooved-surface topography on cellular proliferation of murine bone marrow-derived mesenchymal stem cells. Topographical features of nano- and micro-scales, fabricated by using various biocampatible synthetic and biological macromolecules, have shown potential effects on various cellular processes, including cell division and proliferation among others [ 29 – 31 , 36 ]. In our study, SEM images of microgrooved surfaces revelaed various micro-sized topographical features which were found to have effects on celluar adherence, cell density, morphology, cell division and proliferation.…”

Perlecan Delineates Stem Cell Niches in Human Foetal Hip, Knee and Elbow Cartilage Rudiments and Has Potential Roles in the Regulation of Stem Cell Differentiation

“…Live cell imaging of stem cell niches where the niche is de-stressed results in a change in the stem cell quiescent state to a migratory phenotype which can home to sites of tissue damage [64,65]. This is consistent with roles proposed for biomechanical forces and ECM directive cues in the regulation of stem cell phenotype in vivo and the promotion of wound healing [3,[66][67][68][69].…”

“…The stiffness of biomaterials is an important determinant which drives stem cell proliferation and differentiation [74]. Evaluation of matrices synthesized by human fibroblasts has shown an increase in stem cell proliferation and differentiation, down-regulation of adipogenesis and osteogenesis but promotion of chondrogenesis [69]. In the human foetal elbow the perichondrial stem cell niche is contained in a matrix layed down by fibroblastic cells in the outer regions of the perichondrium.…”