Regulation of fibroblast proliferation in three-dimensional collagen gel matrix

Tadashi Mio, Yuichi Adachi, Debra J. Romberger, Ronald F. Ertl, Stephen I. Rennard

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


Fibroblasts in vivo reside in a three-dimensional (3-D) matrix. The 3-D culture method using collagen gels provides valuable information, but it also has some practical difficulties. In particular, the changes caused by the contraction of gels and the occasional abrupt detachment from the underlying surface have made extended culture difficult. In this study, the 3-D culture method was modified in order to observe the cells with minimal change of substrata for longer periods. The proliferation characteristics of fibroblasts cultured in gels in response to fetal calf serum (FCS), to two defined growth factors, insulin and platelet-derived growth factor (PDGF), and to a growth inhibitory factor, prostaglandin E2 (PGE2), were evaluated with this system in comparison with monolayer cultured fibroblasts. The DNA content of fibroblasts cultured both in gels and on dishes increased in response to FCS in a concentration-dependent manner. The proliferation of gel-cultured fibroblasts, however, was lower than that of dish-cultured cells, and higher concentrations of serum were necessary for proliferation. The response of gel-cultured cells to PDGF was also less than that of dish- cultured cells. In addition, fibroblasts cultured in gel culture did not respond to insulin, while the fibroblasts on dishes responded to insulin in a concentration-dependent manner. In contrast to the reduced response to growth stimulators, PGE2 inhibited proliferation in gel culture and in monolayer culture similarly. The reduced responsiveness to growth stimulation but equivalent response to growth inhibition may account for reduced proliferation of fibroblasts in 3-D culture.

Original languageEnglish (US)
Pages (from-to)427-433
Number of pages7
JournalIn Vitro Cellular and Developmental Biology - Animal
Issue number7
StatePublished - 1996


  • collagen gel
  • fibroblast
  • proliferation
  • wound repair

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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