title: Interaction between osteoarthritic chondrocytes and adipose-derived stem cells is dependent on cell distribution in three-dimension and transforming growth factor-β3 induction.
abstract: Stem cells hold great promise for treating cartilage degenerative diseases such as osteoarthritis (OA). The efficacy of stem cell-based therapy for cartilage repair is highly dependent on their interactions with local cells in the joint. This study aims at evaluating the interactions between osteoarthritic chondrocytes (OACs) and adipose-derived stem cells (ADSCs) using three dimensional (3D) biomimetic hydrogels. To examine the effects of cell distribution on such interactions, ADSCs and OACs were co-cultured in 3D using three co-culture models: conditioned medium (CM), bi-layered, and mixed co-culture with varying cell ratios. Furthermore, the effect of transforming growth factor (TGF)-β3 supplementation on ADSC-OAC interactions and the resulting cartilage formation was examined. Outcomes were analyzed using quantitative gene expression, cell proliferation, cartilage matrix production, and histology. TGF-β3 supplementation led to a substantial increase in cartilage matrix depositions in all groups, but had differential effects on OAC-ADSC interactions in different co-culture models. In the absence of TGF-β3, CM or bi-layered co-culture had negligible effects on gene expression or cartilage formation. With TGF-β3 supplementation, CM and bi-layered co-culture inhibited cartilage formation by both ADSCs and OACs. In contrast, a mixed co-culture with moderate OAC ratios (25% and 50%) resulted in synergistic interactions with enhanced cartilage matrix deposition and reduced catabolic marker expression. Our results suggested that the interaction between OACs and ADSCs is highly dependent on cell distribution in 3D and soluble factors, which should be taken into consideration when designing stem cell-based therapy for treating OA patients.
authors.affiliation: 1 Department of Mechanical Engineering, Stanford University School of Medicine , Stanford, California.
authors.forename: Janice H
authors.initials: JH
authors.lastname: Lai
authors.forename: Heather
authors.initials: H
authors.lastname: Rogan
authors.forename: Glen
authors.initials: G
authors.lastname: Kajiyama
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.forename: R Lane
authors.initials: RL
authors.lastname: Smith
authors.forename: William
authors.initials: W
authors.lastname: Maloney
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects / Q000254:growth & development; D002450:Cell Communication / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020219:Chondrogenesis / Q000187:drug effects; D018920:Coculture Techniques; D024043:Collagen Type II / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D017077:Culture Media, Conditioned; D053782:Transforming Growth Factor beta3