title: Concentration-Dependent hMSC Differentiation on Orthogonal Concentration Gradients of GRGDS and BMP-2 Peptides.
abstract: Self-assembled monolayer substrates containing tethered orthogonal concentration profiles of GRGDS (glycine/arginine/glycine/aspartic acid/serine) and BMP-2 (bone morphogenetic protein) peptides are shown to accelerate or decelerate, depending on the concentrations, the proliferation and osteoblastic differentiation of human mesenchymal stem cell (hMSC) populations in vitro without the use of osteogenic additives in culture medium. Concurrently, the single peptide gradient controls (GRGDS or BMP-2 only) induce significantly different proliferation and differentiation behavior from the orthogonal substrates. Bone sialoprotein (BSP) and Runt-related transcription factor 2 (Runx2) PCR data acquired from hMSC populations isolated by laser capture microdissection correspond spatially and temporally to protein marker data obtained from immunofluorescent imaging tracking of the differentiation process. Although genomic and protein data at high concentrations area GRGDS (71-83 pmol/cm(2)):BMP-2 (25 pmol/cm(2)) reveal an implicit acceleration on the hMSC differentiation timeline relative to the individual peptide concentrations, most of the GRGDS and BMP-2 combinations displayed significant antagonistic behavior during the hMSC differentiation. These data highlight the utility of the orthogonal gradient approach to aid in identifying optimal concentration ranges of translationally relevant peptides and growth factors for targeting cell lineage commitment.
authors.affiliation: Department of Polymer Science and ‡Department of Biomedical Engineering, The University of Akron , Akron, Ohio 44325, United States.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Polymer Science and ‡Department of Biomedical Engineering, The University of Akron , Akron, Ohio 44325, United States.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Policastro
authors.affiliation: Department of Polymer Science and ‡Department of Biomedical Engineering, The University of Akron , Akron, Ohio 44325, United States.
authors.forename: Qiyao
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Polymer Science and ‡Department of Biomedical Engineering, The University of Akron , Akron, Ohio 44325, United States.
authors.forename: Jukuan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Polymer Science and ‡Department of Biomedical Engineering, The University of Akron , Akron, Ohio 44325, United States.
authors.forename: Robin
authors.initials: R
authors.lastname: Jacquet
authors.affiliation: Department of Polymer Science and ‡Department of Biomedical Engineering, The University of Akron , Akron, Ohio 44325, United States.
authors.forename: William J
authors.initials: WJ
authors.lastname: Landis
authors.affiliation: Department of Polymer Science and ‡Department of Biomedical Engineering, The University of Akron , Akron, Ohio 44325, United States.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Becker
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000378:metabolism; D061346:Laser Capture Microdissection; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D003470:Culture Media; D058574:Integrin-Binding Sialoprotein; D009842:Oligopeptides; C493709:RUNX2 protein, human; C049554:glycyl-arginyl-glycyl-aspartyl-serine