Optimal combination of soluble factors for tissue engineering of permanent cartilage from cultured human chondrocytes

Guangyao Liu, Hiroshi Kawaguchi, Toru Ogasawara, Yukiyo Asawa, Junji Kishimoto, Tsuguharu Takahashi, Ung Il Chung, Hisayo Yamaoka, Hirotaka Asato, Kozo Nakamura, Tsuyoshi Takato, Kazuto Hoshi

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)


Since permanent cartilage has poor self-regenerative capacity, its regeneration from autologous human chondrocytes using a tissue engineering techniquemaygreatly benefit the treatment of various skeletal disorders. However, the conventional autologous chondrocyte implantation is insufficient both in quantity and in quality due to two major limitations: dedifferentiation during a long term culture for multiplication and hypertrophic differentiation by stimulation for the redifferentiation. To overcome the limitations, this study attempted to determine the optimal combination in primary human chondrocyte cultures under a serum-free condition, from among 12 putative chondrocyte regulators. From the exhaustive 212 = 4,096 combinations, 256 were selected by fractional factorial design, and bone morphogenetic protein-2 and insulin (BI) were statistically determined to be the most effective combination causing redifferentiation of the dedifferentiated cells after repeated passaging. Wefurther found that the addition of triiodothyronine (T3) prevented the BI-induced hypertrophic differentiation of redifferentiated chondrocytes via the suppression of Akt signaling. The implant formed by the human chondrocytes cultured in atelocollagen and poly(L-latic acid) scaffold under the BI + T3 stimulation consisted of sufficient hyaline cartilage with mechanical properties comparable with native cartilage after transplantation in nude mice, indicating that BI + T3 is the optimal combination to regenerate a clinically practical permanent cartilage from autologous chondrocytes.

Original languageEnglish
Pages (from-to)20407-20415
Number of pages9
JournalJournal of Biological Chemistry
Issue number28
Publication statusPublished - Jul 13 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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