Oxygen tension differentially regulates the functional properties of cartilaginous tissues engineered from infrapatellar fat pad derived MSCs and articular chondrocytes

Periodical: Osteoarthritis and Cartilage ISBN: 1522-9653 (Electronic) 1063-4584 (Linking)  Date: 2010/07/24  Language: Eng

Authors:Buckley, C. T., Vinardell, T., Kelly, D. J.

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Abstract
BACKGROUND: For current tissue engineering or regenerative medicine strategies, chondrocyte- or mesenchymal stem cell (MSC)-seeded constructs are typically cultured in normoxic conditions (20% oxygen). However, within the knee joint capsule a lower oxygen tension exists. OBJECTIVE: The objective of this study was to investigate how chondrocytes and infrapatellar fad pad derived MSCs will respond to a low oxygen (5%) environment in 3D agarose culture. Our hypothesis was that culture in a low oxygen environment (5%) will enhance the functional properties of cartilaginous tissues engineered using both cell sources. EXPERIMENTAL DESIGN: Cell-encapsulated agarose hydrogel constructs (seeded with chondrocytes or infrapatellar fat pad derived MSCs) were prepared and cultured in a chemically defined serum-free medium in the presence (chondrocytes and MSCs) or absence (chondrocytes only) of transforming growth factor-beta3 (TGF-beta3) in normoxic (20%) or low oxygen (5%) conditions for 42 days. Constructs were assessed at days 0, 21 and 42 in terms of mechanical properties, biochemical content and histologically. RESULTS: Low oxygen tension (5%) was observed to promote extracellular matrix production by chondrocytes cultured in the absence of TGF-beta3, but was inhibitory in the presence of TGF-beta3. In contrast, a low oxygen tension enhanced chondrogenesis of infrapatellar fat pad constructs in the presence of TGF-beta3, leading to superior mechanical functionality compared to chondrocytes cultured in identical conditions. CONCLUSIONS: Extrapolating the results of this study to the in vivo setting, it would appear that joint fat pad derived MSCs may possess a superior potential to generate a functional repair tissue in low oxygen tensions. However, in the context of in vitro cartilage tissue engineering, chondrocytes maintained in normoxic conditions in the presence of TGF-beta3 generate the most mechanically functional tissue.