title: Induction of chondrogenic differentiation in mesenchymal stem cells by TGF-beta cross-linked to collagen-PLLA [poly(L-lactic acid)] scaffold by transglutaminase 2.
abstract: Transglutaminase-mediated cross-linking has been employed to optimize the mechanical properties and stability of tissue scaffolds. We have characterized tissue transglutaminase (TG2)-mediated cross-linking as a useful tool to deliver biologically-active TGF to mesenchymal stem cells (MSCs) and direct their differentiation towards a chondrogenic lineage. TGF-β3 is irreversibly cross-linked by TG2 to collagen type II-coated poly(L-lactic acid) nanofibrous scaffolds and activates Smad phosphorylation and Smad-dependent expression of a luciferase reporter. Human bone marrow-derived MSCs cultured on these scaffolds deposit cartilaginous matrix after 14 days of culture at 50 % efficiency compared to chondrogenesis in the presence of soluble TGF-β3. These findings are significant because they suggest a novel approach for the programming of MSCs in a spatially controlled manner by immobilizing biologically active TGF-β3 via cross-linking to a collagen-coated polymeric scaffold.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD, USA, corinneniger@hotmail.com.
authors.forename: Corinne
authors.initials: C
authors.lastname: Niger
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Beazley
authors.forename: Maria
authors.initials: M
authors.lastname: Nurminskaya
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D020219:Chondrogenesis / Q000187:drug effects*; D003094:Collagen / Q000737:chemistry*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D055767:Immobilized Proteins; D011091:Polyesters; D011108:Polymers; D016212:Transforming Growth Factor beta; D019344:Lactic Acid; C033616:poly(lactide); D003094:Collagen; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
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