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The regulation of epithelial cell proliferation and growth by IL-1 receptor antagonist

Makoto Kondo1, Masayuki Yamato, Ryo Takagi

  • 1Graduate School of Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.

Biomaterials
|October 13, 2012
PubMed

Insights

Identifying growth factors is key for reproducible epithelial cell sheets in regenerative medicine. Interleukin-1 receptor antagonist (IL-1RA) and anti-IL-1α antibody promote cell growth and differentiation.

Area of Science:

  • Regenerative Medicine
  • Tissue Engineering
  • Cell Biology

Background:

  • Clinical translation of epithelial cell sheets for cornea and esophagus treatment has been performed.
  • Preclinical studies revealed species-specific variations in epithelial cell growth potential.
  • Canine epithelial cells showed robust growth, while rat cells exhibited poor growth under feeder-free conditions.

Purpose of the Study:

  • To identify specific growth-promoting factors for epithelial cells.
  • To understand the molecular mechanisms behind species-specific growth differences.
  • To optimize conditions for fabricating transplantable epithelial cell sheets.

Main Methods:

  • Analysis of conditioned medium from canine cell cultures at various time points.
  • Quantitative evaluation of time-dependent gene expression for forty growth factors.
  • Assay of growth-promoting and inhibitory activities of specific factors and antibodies on rat and human epithelial cells.

Main Results:

  • Conditioned medium exhibited time-dependent growth promotive activity for rat epithelial cells.
  • Interleukin-1 receptor antagonist (IL-1RA) showed statistically significant promotive activity.
  • Interleukin-1 alpha (IL-1α) demonstrated significant inhibitory activity, which was reversed by neutralizing anti-IL-1α antibody.
  • IL-1RA and anti-IL-1α antibody promoted proliferation and differentiation of human epidermal keratinocytes.

Conclusions:

  • IL-1RA and IL-1α play critical roles in regulating epithelial cell growth and differentiation.
  • These findings provide insights for fabricating reproducible, transplantable epithelial cell sheets for regenerative medicine.
  • The study highlights the potential of using IL-1RA and anti-IL-1α for optimizing cell sheet engineering.

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