title: GFOGER-modified MMP-sensitive polyethylene glycol hydrogels induce chondrogenic differentiation of human mesenchymal stem cells.
abstract: The cellular microenvironment plays a crucial role in directing proliferation and differentiation of stem cells. Cells interact with their microenvironment via integrins that recognize certain peptide sequences of extracellular matrix proteins. This receptor-ligand binding has profound impact on cell fate. Interactions of human bone marrow mesenchymal stem cells (hMSCs) with the triple helical collagen mimetic, GPC(GPP)5-GFOGER-(GPP)5GPC-NH2, and the fibronectin adhesion peptide, RGD, were studied in degradable or nondegradable polyethylene glycol (PEG) gels formed by Michael-type addition chemistry. Proliferation, cytoskeletal morphology, and chondrogenic differentiation of encapsulated hMSCs were evaluated. The hMSCs adopted a highly spread morphology within the GFOGER-modified gels, whereas RGD induced a star-like spreading of the cells. hMSCs within GFOGER-modified degradable gels had a high proliferation rate compared with cells in peptide-free gels (p=0.017). Gene expression of type II collagen was highest in GFOGER-modified degradable gels after 21 days. Peptide incorporation increased GAG production in degradable gels after 7 and 21 days and GFOGER-modified degradable hydrogels had on average the highest GAG content, a finding that was confirmed by Alcian blue staining. In conclusion, the GFOGER peptide enhances proliferation in degradable PEG gels and provides a better chondrogenic microenvironment compared with the RGD peptide.
authors.affiliation: Cartilage Engineering+Regeneration Laboratory , ETH Zürich, Zürich, Switzerland .
authors.forename: Rami
authors.initials: R
authors.lastname: Mhanna
authors.forename: Ece
authors.initials: E
authors.lastname: Öztürk
authors.forename: Queralt
authors.initials: Q
authors.lastname: Vallmajo-Martin
authors.forename: Christopher
authors.initials: C
authors.lastname: Millan
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.forename: Marcy
authors.initials: M
authors.lastname: Zenobi-Wong
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D019245:Compressive Strength / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D013194:Staining and Labeling
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D006025:Glycosaminoglycans; D020100:Hydrogels; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen; D004247:DNA; D020782:Matrix Metalloproteinases