title: Pharmacological modulation of human mesenchymal stem cell chondrogenesis by a chemically oversulfated polysaccharide of marine origin: potential application to cartilage regenerative medicine.
abstract: Mesenchymal stem cells (MSCs) are considered as an attractive source of cells for cartilage engineering due to their availability and capacity for expansion and multipotency. Differentiation of MSC into chondrocytes is crucial to successful cartilage regeneration and can be induced by various biological agents, including polysaccharides that participate in many biological processes through interactions with growth factors. Here, we hypothesize that growth factor-induced differentiation of MSC can be increased by chemically oversulfated marine polysaccharides. To test our hypothesis, human adipose tissue-derived MSCs (hATSCs) were cultured in pellets with transforming growth factor (TGF)-β1-supplemented chondrogenic medium containing either the polysaccharide GY785 DR or its oversulfated isoform GY785 DRS. Chondrogenesis was monitored by the measurement of pellet volume, quantification of DNA, collagens, glycosaminoglycans (GAGs), and immunohistological staining. Our data revealed an increase in pellet volume, total collagens, and GAG production with GY785 DRS and chondrogenic medium. The enhanced chondrogenic differentiation of hATSC was further demonstrated by the increased expression of several chondrogenic markers by real-time reverse transcription-polymerase chain reaction. In addition, surface plasmon resonance analyses revealed that TGF-β1 bound GY785 DRS with higher affinity compared to GY785 DR. In association with TGF-β1, GY785 DRS was found to upregulate the phosphorylation of extracellular signal-regulated kinase 1/2, indicating that oversulfated polysaccharide affects the mitogen activated protein kinase signaling activity. These results demonstrate the upregulation of TGF-β1-dependent stem cell chondrogenesis by a chemically oversulfated marine polysaccharide. This polysaccharide of marine origin is easily producible and therefore could be considered a promising additive to drive efficient and reliable MSC chondrogenesis for cartilage tissue engineering.
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 791 Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Group STEP Skeletal Tissue Engineering and Physiopathology, Université de Nantes, Nantes, France.
authors: Christophe
authors: C
authors: Merceron
authors: Sophie
authors: S
authors: Portron
authors: Caroline
authors: C
authors: Vignes-Colombeix
authors: Emilie
authors: E
authors: Rederstorff
authors: Martial
authors: M
authors: Masson
authors: Julie
authors: J
authors: Lesoeur
authors: Sophie
authors: S
authors: Sourice
authors: Corinne
authors: C
authors: Sinquin
authors: Sylvia
authors: S
authors: Colliec-Jouault
authors: Pierre
authors: P
authors: Weiss
authors: Claire
authors: C
authors: Vinatier
authors: Jérôme
authors: J
authors: Guicheux
mesh_terms: D052436:Adipose Tissue, White / Q000166:cytology*; D000943:Antigens, Differentiation / Q000378:metabolism; D002356:Cartilage / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D012038:Regeneration; D044968:Regenerative Medicine; D015398:Signal Transduction; D023822:Tissue Engineering; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000502:physiology
chemical_list: D000943:Antigens, Differentiation; C572701:GY785 DR; C572702:GY785 DRS; D007328:Insulin; D011134:Polysaccharides; D053773:Transforming Growth Factor beta1