![]() The rotary cell culture system (RCCS) bioreactor, developed by the National Aeronautics and Space Administration (NASA), as a tool to simulate microgravity has been shown to provide a relatively well-defined fluid dynamic environment with efficient mass transfer for nutrients and gases and low shear stress for tissue growth. 32 Hypoxia stimulated chondrogenic differentiation of bone marrow-derived MSCs by induction of TGF-β1 gene expression and protein production. Diverse types of mechanical stimuli, including compressive load, 26 simulated microgravity (SMG), 30 low-intensity pulsed ultrasound, 27, 28, 31 and hydrostatic pressure has been reported to induce or regulate the differentiation of MSCs through TGF-β signaling pathway. 26– 28 TGF-β1 and TGF-β3, members of the TGF-β superfamily, that promote fibro-chondrogenic differentiation of MSCs 29 and production of meniscus-like ECM. The differentiation of multiple types of MSCs is influenced by a wide range of biochemical, 24 microenvironmental, 25 and mechanical factors. Supplementation of primary MC with knee infrapatellar fat pad derived MSCs may be a better anatomical option. 21, 23 However, the use of bone marrow MSCs potentially presents another anatomical site other than the knee for MSCs harvest. 18, 19 Supplementation of primary MC through direct coculture with bone marrow mesenchymal stem cells (MSCs) has been demonstrated as a strategy to retain the differentiated phenotype of primary MC with the additional benefits of synergistic production of the functional matrix components of the meniscus 20– 22 and downregulation of hypertrophic differentiation of MSCs. However, expanded MC suffer from dedifferentiation and loss of the functional matrix-forming phenotype of native MC. 18, 19 To circumvent this limitation, primary MC are expanded in in vitro culture. 1, 16, 17 Obtaining sufficient numbers of primary MC for meniscus tissue engineering is often impossible and impractical. 5– 15 Primary meniscus cells (MC) are the ideal cell sources as they closely resemble the in vivo phenotype of MC and can form the biomechanically functional extracellular matrix (ECM) of the meniscus. 3, 4 Tissue engineering using cells presents a potential option to create functional tissues to replace damaged meniscus. 3, 4 However, partial meniscectomy is a major risk factor for the early development of knee osteoarthritis. 1 Treatment options for these tears are currently limited to partial meniscectomy. ![]() 2 Traumatic tears in the avascular region of the tissue are common and do not heal. 1 They primarily serve as mechanical load distributors within the knee joint. The menisci of the knee are a pair of fibrocartilaginous tissues. ![]()
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