title: Glycosaminoglycans mimetics potentiate the clonogenicity, proliferation, migration and differentiation properties of rat mesenchymal stem cells.
abstract: Successful use of stem cell-based therapeutic products is conditioned by transplantation of optimized cells in permissive microenvironment. Mesenchymal stem cell (MSC) fates are tightly regulated by humoral factors, cellular interactions and extracellular matrix (ECM) components, such as glycosaminoglycans (GAG), which are complex polysaccharides with structural heterogeneity. During osteogenesis, a temporally controlled expression of particular GAG species is required to interact with specific growth promoting and differentiating factors to regulate their biological activities. As a comparative tool to study natural GAG, we used structurally and functionally related synthetic GAG mimetics. One of these compounds [OTR(4120)] was previously shown to stimulate bone repair in rat models. Here, we demonstrate that structurally distinct GAG mimetics stimulate differentially clonogenicity, proliferation, migration and osteogenic phenotype of MSC in vitro, according to their specific chemical signature, underlying the role of sulfate and acetyl groups in specific interactions with heparin binding factors (HBF). These effects are dependent on FGF-2 interactions since they are inhibited by a FGF receptor 1 signaling pathway blocker. These data suggest that the in vivo [OTR(4120)] bone regenerative effect could be due to its ability to induce MSC migration and osteogenic differentiation. To conclude, we provide evidences showing that GAG mimetics may have great interest for bone regeneration therapy and represent an alternative to exogenous growth factor treatments to optimize potential therapeutic properties of MSC.
authors.affiliation: Université Paris Est Créteil, Faculté des Sciences et Technologie, F-94010, Créteil, France.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Frescaline
authors.forename: Thibault
authors.initials: T
authors.lastname: Bouderlique
authors.forename: Minh Bao
authors.initials: MB
authors.lastname: Huynh
authors.forename: Dulce
authors.initials: D
authors.lastname: Papy-Garcia
authors.forename: José
authors.initials: J
authors.lastname: Courty
authors.forename: Patricia
authors.initials: P
authors.lastname: Albanese
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005434:Flow Cytometry; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D016222:Fibroblast Growth Factor 2; D006493:Heparin