title: Trophic stimulation of articular chondrocytes by late-passage mesenchymal stem cells in coculture.
abstract: Coculture of mesenchymal stem cells (MSCs) with articular chondrocytes (ACs) increases glycosaminoglycan (GAG) accumulation compared to monoculture. MSCs might (1) differentiate into ACs (progenitor role) and/or (2) stimulate AC matrix metabolism (trophic role). MSCs lose the ability to undergo chondrogenesis after extended passaging. We hypothesized that MSCs act predominantly as progenitors, and that late-passage MSCs without chondrogenic potential would be unable to increase GAG in coculture. Early- and late-passage human MSCs (hMSCs) were grown in pellet monoculture under chondrogenic conditions and in pellet coculture with bovine ACs. Chondrogenesis was assessed with GAG quantification, safranin-O staining, and quantitative PCR (qPCR). Contributions of human and bovine cells were assessed with species-specific qPCR and human-specific immunostaining. Late-passage hMSCs did not undergo chondrogenesis in monoculture with chondrogenic stimuli or in coculture with ACs. Early-passage hMSCs underwent chondrogenesis only in response to chondrogenic stimuli. Coculture pellets in both cases accumulated as much GAG/DNA as monoculture AC pellets. Aggrecan transcription was not increased in coculture. Late-passage hMSCs that do not undergo chondrogenesis are capable of stimulating GAG accumulation in coculture with ACs. This supports a trophic effect of hMSCs on ACs. hMSCs may have therapeutic utility even after prolonged passaging.
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, CA.
authors.forename: Miqi
authors.initials: M
authors.lastname: Wang
authors.forename: Ruyan
authors.initials: R
authors.lastname: Rahnama
authors.forename: Tiffany
authors.initials: T
authors.lastname: Cheng
authors.forename: Eva
authors.initials: E
authors.lastname: Grotkopp
authors.forename: Linsey
authors.initials: L
authors.lastname: Jacobs
authors.forename: Sonja
authors.initials: S
authors.lastname: Limburg
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Kim
authors.forename: Alfred C
authors.initials: AC
authors.lastname: Kuo
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology*; D002417:Cattle; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D020219:Chondrogenesis; D018920:Coculture Techniques; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D013045:Species Specificity
chemical_list: D006025:Glycosaminoglycans
keywords: chondrogenesis; coculture; mesenchymal stem cells; trophic