title: Transferable cell-secreted extracellular matrices enhance osteogenic differentiation.
abstract: The coating of synthetic biomaterials with cell-derived decellularized extracellular matrices (DMs) represents a promising approach to confer bioactivity to otherwise inert materials and direct cell fate of host or transplanted cells. These coatings are typically deposited on biomaterials by culturing matrix-depositing cells for a sufficient duration on the target, followed by decellularization of the substrate. We hypothesized that DMs created in monolayer culture could be collected and then transferred to a secondary substrate while retaining their instructive potential. Transferred decellularized matrices (tDMs) were created by culturing human mesenchymal stem cells (hMSCs) on tissue culture plastic (TCP) under a controlled microenvironment to deposit a highly osteogenic DM, followed by collection, mechanical homogenization and transfer to a secondary culture surface. We then investigated its capacity to accelerate naïve hMSC osteogenic differentiation by quantifying gene expression, intracellular alkaline phosphatase production, and calcium deposition when cultured on DMs or tDMs. All markers were significantly higher in hMSCs seeded on DMs or tDMs compared to cells on TCP. The osteogenic response of naïve hMSCs to tDMs was dose dependent. We observed a reduction in ERK phosphorylation in hMSCs, as well as a possible role of the cell surface integrin α2β1, when probing the mode of efficacy for tDMs. This study represents a proof-of-principle that cell-derived matrix coatings can be deposited and effectively transferred while retaining the ability to instruct cell phenotype, thus offering a novel approach toward the development of hybrid biomaterials that mimic the complex interactions between cells and the extracellular matrix.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Decaris
authors.forename: Azad
authors.initials: A
authors.lastname: Mojadedi
authors.forename: Archana
authors.initials: A
authors.lastname: Bhat
authors.forename: J Kent
authors.initials: JK
authors.lastname: Leach
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000880:Anthraquinones / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D048430:Cell Shape; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism; D042541:Intracellular Space / Q000201:enzymology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D010012:Osteogenesis; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000880:Anthraquinones; D016023:Integrins; C010078:alizarin; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase