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Published Online: 4 February 2015

Interaction Between Osteoarthritic Chondrocytes and Adipose-Derived Stem Cells Is Dependent on Cell Distribution in Three-Dimension and Transforming Growth Factor-β3 Induction

Publication: Tissue Engineering Part A
Volume 21, Issue Number 5-6

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.

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Information & Authors

Information

Published In

cover image Tissue Engineering Part A
Tissue Engineering Part A
Volume 21Issue Number 5-6March 2015
Pages: 992 - 1002
PubMed: 25315023

History

Published in print: March 2015
Published ahead of print: 6 February 2015
Published online: 4 February 2015
Published ahead of production: 15 October 2014
Accepted: 6 October 2014
Received: 29 April 2014

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Authors

Affiliations

Janice H. Lai
Department of Mechanical Engineering, Stanford University School of Medicine, Stanford, California.
Heather Rogan
Department of Bioengineering, Stanford University School of Medicine, Stanford, California.
Glen Kajiyama
Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California.
Stuart B. Goodman
Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California.
R. Lane Smith
Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California.
William Maloney
Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California.
Fan Yang
Department of Bioengineering, Stanford University School of Medicine, Stanford, California.
Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California.

Notes

Address correspondence to:Fan Yang, PhDDepartment of Orthopaedic SurgeryStanford University School of Medicine300 Pasteur Dr., Edwards R105Stanford, CA 94305-5341E-mail: [email protected]

Disclosure Statement

The authors declared no conflicts of interest.

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