Pharmacological Modulation of Human Mesenchymal Stem Cell Chondrogenesis by a Chemically Oversulfated Polysaccharide of Marine Origin: Potential Application to Cartilage Regenerative Medicine
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 biolog...
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Published in | Stem cells (Dayton, Ohio) Vol. 30; no. 3; pp. 471 - 480 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.03.2012
Oxford University Press AlphaMed Press |
Subjects | |
Online Access | Get full text |
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Summary: | 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. STEM CELLS 2012;30:471–480 |
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Bibliography: | foundation Arthritis Courtin Author contributions: C.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.P.: collection and/or assembly of data, data analysis and interpretation; C.V.-C., M.M., J.L., and S.S.: collection and/or assembly of data; E.R.: conception and design, collection and/or assembly of data, manuscript writing; C.S.: provision of study material or patients; S.C.-J.: financial support, provision of study material or patients, final approval of the manuscript; P.W.: financial support, final approval of the manuscript; C.V.: data analysis and interpretation, final approval of the manuscript; and J.G.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of the manuscript. Société Française de Rhumatologie ANR Tecsan project First published online in STEM CELLSEXPRESS November 30, 2011. ANR, young researchers project ark:/67375/WNG-HWQ2QGSX-W Disclosure of potential conflicts of interest is found at the end of this article. IFREMER INSERM - No. U791 ArticleID:STEM1686 fondation de l'avenir pour la recherche médicale appliquée - No. ET7-451; No. ET9-491 istex:F39500FEF00EF7F8022C31690C293F9CFD4AEA22 First published online in S Author contributions: C.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.P.: collection and/or assembly of data, data analysis and interpretation; C.V.‐C., M.M., J.L., and S.S.: collection and/or assembly of data; E.R.: conception and design, collection and/or assembly of data, manuscript writing; C.S.: provision of study material or patients; S.C.‐J.: financial support, provision of study material or patients, final approval of the manuscript; P.W.: financial support, final approval of the manuscript; C.V.: data analysis and interpretation, final approval of the manuscript; and J.G.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of the manuscript. C XPRESS E Telephone: +33 240412919; Fax: +33 240083712 November 30, 2011. TEM ELLS |
ISSN: | 1066-5099 1549-4918 |
DOI: | 10.1002/stem.1686 |