Abstract
As an alternative to chondrocytes-based cartilage repair, stem cell-based therapies have been investigated. Specifically, human synovium-derived stem cells (hSSCs) are a promising cell source based on their highly capacities for chondrogenesis, but some methodological improvements are still required towards optimal cartilage regeneration. Recently, a small compound, TD-198946, was reported to promote chondrogenesis of several stem cells, but the effect on hSSCs is still unknown. This study aimed to examine the effects of TD-198946 on chondrocyte differentiation and cartilaginous tissue formation with hSSCs. A range of concentrations of TD-198946 were examined in chondrogenic cultures of hSSC-derived cell pellets. The effect of TD-198946 on glycosaminoglycan (GAG) production, chondrocyte marker expression, and cartilaginous tissue formation was assessed. At concentrations >1nM, TD-198946 dose-dependently enhanced GAG production, particularly hyaluronan, whereas chondrocyte differentiation was not impacted. When combined with transforming growth factor β3 (TGFβ3), TD-198946 promoted chondrocyte differentiation and production of cartilaginous matrices at doses <1nM as judged by SOX9, S100, and type 2 collagen upregulation. Conversely, doses >1nM TD-198946 attenuated TGFβ3-associated chondrocyte differentiation, but aggrecan was efficiently produced at 1 to 10nM TD-198946 as judged by safranin O staining. Thus, TD-198946 exhibited different dose ranges for either GAG synthesis or chondrocyte differentiation. Regarding use of TD-198946 for in vitro engineering of cartilage, cartilaginous particles rich in type 2 collagen and GAG were predominately created with TGFβ3+0.25nM TD-198946. These studies have demonstrated that TD-198946 synergistically enhances chondrogenesis of hSSCs in a unique dose range, and such findings may provide a novel strategy for stem cell-based cartilage therapy.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of tissue engineering and regenerative medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
