Synergistic effects of FGF-2 with insulin or IGF-I on the proliferation of human auricular chondrocytes

Tsuguharu Takahashi, Toru Ogasawara, Junji Kishimoto, Guangyao Liu, Hirotaka Asato, Takashi Nakatsuka, Eijyu Uchinuma, Kozo Nakamura, Hiroshi Kawaguchi, Tsuyoshi Takato, Kazuto Hoshi

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57 Citations (Scopus)

Abstract

Chondrocyte preparation with the safety and efficiency is the first step in cartilage regenerative medicine. To prepare a chondrocyte proliferation medium that does not contain fetal bovine serum (FBS) and that provides more than a 1000-fold increase in cell numbers within approximately 1 month, we attempted to use the medium containing 5% human serum (HS), but it exerted no more than twofold increase in 2 weeks. To compensate for the limited proliferation ability in HS, we investigated the combinational effects of 12 factors [i.e., fibroblast growth factor(FGF)-2, insulin-like growth factor(IGF)-I, insulin, bone morphogenetic protein-2, parathyroid hormone, growth hormone, dexamethasone, 1α25-dihydroxy vitamin D3, L-3,3′, 5′-triodothyronine, interleukine-1 receptor antagonist, 17β-estradiol, and testosterone] on the proliferation of human auricular chondrocytes by analysis of variance in fractional factorial design. As a result, FGF-2, dexamethasone, insulin, and IGF-I possessed promotional effects on proliferation, while the combination of FGF-2 with insulin or IGF-I synergistically enhanced the proliferation. Actually, the chondrocytes increased 7.5-fold in number in 2 weeks in a medium containing 5% HS with 10 ng/ml FGF-2, while the cell number synergistically gained a 10-12-fold increase with 5 μg/ml insulin or 100 ng/ml IGF-I in the same period. The proliferation effects were more enhanced at a concentration of 100 ng/ml for FGF-2, and especially for the combination of 100 ng/ml FGF-2 and 5 μg/ml insulin (approximately 16-fold within 2 weeks). In the long-term culture with repeated passaging, this combination provided more than 10,000-fold within 8 weeks (i.e., passage 4). Thus, we concluded that such a combination of FGF-2 with insulin or IGF-I may be useful for promotion of auricular chondrocyte proliferation in a clinical application for cartilage regeneration.

Original languageEnglish
Pages (from-to)683-693
Number of pages11
JournalCell Transplantation
Volume14
Issue number9
DOIs
Publication statusPublished - Dec 1 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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    Takahashi, T., Ogasawara, T., Kishimoto, J., Liu, G., Asato, H., Nakatsuka, T., Uchinuma, E., Nakamura, K., Kawaguchi, H., Takato, T., & Hoshi, K. (2005). Synergistic effects of FGF-2 with insulin or IGF-I on the proliferation of human auricular chondrocytes. Cell Transplantation, 14(9), 683-693. https://doi.org/10.3727/000000005783982675