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. 2006 Jul;78(1):73-85.
doi: 10.1002/jbm.a.30686.

Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM ligands and controls their osteogenic differentiation

Sara R Chastain  1 , Anup K Kundu, Sanjay Dhar, Jay W Calvert, Andrew J Putnam
Affiliations

Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM ligands and controls their osteogenic differentiation

Sara R Chastain et al. J Biomed Mater Res A. 2006 Jul.

Abstract

The osteogenic potential of mesenchymal stem cells (MSCs) cultured on poly(lactide-co-glycolide) (PLGA) or poly(caprolactone) (PCL), two widely used polymeric biomaterials that have been reported to differentially support osteogenic differentiation, was compared in these studies. Here we report that MSCs cultured in 3-D PLGA scaffolds for up to 5 weeks significantly upregulate osteocalcin gene expression levels. By contrast, osteocalcin expression was markedly downregulated in 3-D PCL-based constructs over the same time course. We hypothesized that differential adsorption of extracellular matrix (ECM) proteins present in serum-containing culture medium and subsequent differences in integrin-mediated adhesion are responsible for these differences, and tested this hypothesis using thin (2-D) polymeric films. Supporting this hypothesis, significant amounts of fibronectin and vitronectin deposited onto both materials in serum-containing osteogenic media, with type-I collagen present in lower amounts. Adhesion-blocking studies revealed that MSCs adhere to PCL primarily via vitronectin, while type-I collagen mediates their attachment to PLGA. These adhesive mechanisms correlated with higher levels of alkaline phosphatase (ALP) activity after 2 weeks of monolayer culture on PLGA versus PCL. These data suggest that the initial adhesion of MSCs to PLGA via type-I collagen fosters osteogenesis while adhesion to PCL via vitronectin does not, and stress the need for an improved molecular understanding of cell-ECM interactions in stem cell-based therapies.

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