title: Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM ligands and controls their osteogenic differentiation.
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.
authors.affiliation: Department of Biomedical Engineering, University of California, Irvine, Irvine, California 92697, and Long Beach Venterans Affairs Healthcare System 90822, USA.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Chastain
authors.forename: Anup K
authors.initials: AK
authors.lastname: Kundu
authors.forename: Sanjay
authors.initials: S
authors.lastname: Dhar
authors.forename: Jay W
authors.initials: JW
authors.lastname: Calvert
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Putnam
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D019344:Lactic Acid; D008024:Ligands; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013997:Time Factors
chemical_list: D016326:Extracellular Matrix Proteins; D008024:Ligands; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid