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Cell sheet technology combined with TD-198946

Towards a treatment for osteoarthritis


Graduate School of Medicine / Faculty of Medicine
Graduate School of Engineering / Faculty of Engineering

Articular cartilage is a permanent tissue with poor self-regenerative capacity. Consequently, a tissue engineering approach to cartilage regenerative therapy could greatly advance the current treatment options for patients with cartilage degeneration and/or defects. Project Research Associate Fumiko Yano and Prof. Ung-il Chung and their colleagues at the Graduate School of Engineering and Graduate School of Medicine, previously reported that direct injection of the thienoindazole derivative, TD-198946, into the knee joints of mice halted the progression of osteoarthritis; the compound induced chondrogenic differentiation without promoting endochondral ossification. In the present study, the researchers applied TD-198946 to a cell-based cartilage reconstruction model, taking advantage of cell-sheet technology (Cell Seed Inc.). The transplanted cell-sheets with TD-198946 were then successfully used to promote the reconstruction of permanent cartilage, with no evidence of chondrocyte hypertrophy in the knee articular cartilage defects created in mice and canines.

© Fumiko Yano. Eight weeks after transplantation, TD-198946-treated cell-sheets enabled the formation of cartilage tissue, as observed with positive safranin O staining (red), in mouse knees.

This study has demonstrated cell-sheet technology combined with TD-198946, a non-conventional technique that realizes articular cartilage reconstruction without scaffolds or cytokines, thus achieving a significant step forward in the treatment of osteoarthritis.

Press release


Fumiko Yano, Hironori Hojo, Shinsuke Ohba, Taku Saito, Muneki Honnami, Manabu Mochizuki, Tsuyoshi Takato, Hiroshi Kawaguchi, Ung-il Chung,
“Cell-sheet technology combined with a thienoindazole derivative small compound TD-198946 for cartilage regeneration”,
Biomaterials Online Edition: 2013/4/24, doi: 10.1016/j.biomaterials.2013.04.008.
Article link


Graduate School of Engineering

Department of Bioengineering, Graduate School of Engineering

Graduate School of Medicine

Graduate School of Medicine Skeletal Development and Regeneration Research Group

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