Chondrogenic Differentiation of Cultured Human Mesenchymal Stem Cells from Marrow

• Published in: Tissue engineering Vol. 4; no. 4; pp. 415 - 428
• Main Authors: Mackay, Alastair M., Beck, Stephen C., Murphy, J. Mary, Barry, Frank P., Chichester, Clinton O., Pittenger, Mark F.
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.12.1998
• Subjects: Adult; Aggrecans; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Cartilage - cytology; Cartilage - metabolism; Cell Differentiation - drug effects; Cells, Cultured; Collagen - biosynthesis; Dexamethasone - pharmacology; Extracellular Matrix - metabolism; Extracellular Matrix Proteins; Humans; Lectins, C-Type; Mesoderm - cytology; Mesoderm - drug effects; Mesoderm - metabolism; Original Articles; Proteoglycans - biosynthesis; Thyroxine - pharmacology; Transforming Growth Factor beta - pharmacology
• ISSN: 1076-3279; 1557-8690
• DOI: 10.1089/ten.1998.4.415

In the adult human, mesenchymal stem cells (MSCs) resident in bone marrow retain the capacity to proliferate and differentiate along multiple connective tissue lineages, including cartilage. In this study, culture-expanded human MSCs (hMSCs) of 60 human donors were induced to express the morphology and gene products of chondrocytes. Chondrogenesis was induced by culturing hMSCs in micromass pellets in the presence of a defined medium that included 100 nM dexamethasone and 10 ng/ml transforming growth factor- β 3 (TGF- β 3 ). Within 14 days, cells secreted an extracellular matrix incorporating type II collagen, aggrecan, and anionic proteoglycans. hMSCs could be further differentiated to the hypertrophic state by the addition of 50 nM thyroxine, the withdrawal of TGF- β 3 , and the reduction of dexamethasone concentration to 1 nM. Increased understanding of the induction of chondrogenic differentiation should lead to further progress in defining the mechanisms responsible for the generation of cartilaginous tissues, their maintenance, and their regeneration.