Keloid tissue analysis discredits a role for myofibroblasts in disease pathogenesis

Rachel E Bell1, Tanya J Shaw1

  • 1Centre for Inflammation Biology & Cancer Immunology, Department of Inflammation Biology, School of Immunology & Microbial Sciences, King's College London, London, UK.

Insights

Keloid scars may not require alpha-smooth muscle actin (αSMA)-positive myofibroblasts, challenging current understanding. This finding suggests that focusing on αSMA as a keloid severity biomarker hinders therapeutic development.

Area of Science:

  • Dermatology
  • Pathology
  • Cell Biology

Background:

  • Myofibroblasts are key effector cells in scar formation and fibrosis.
  • Keloid scars are pathological skin scars with poorly understood mechanisms, often assumed to involve myofibroblasts.

Purpose of the Study:

  • To investigate the presence and role of alpha-smooth muscle actin (αSMA)-positive myofibroblasts in keloid scars.
  • To re-evaluate the current understanding of keloid pathogenesis and its relationship to other scar types.

Main Methods:

  • Analysis of primary and published transcriptional data.
  • Histological examination of keloid lesions.
  • Quantification of αSMA-positive cells in keloid, hypertrophic, and normal scars.

Main Results:

  • Myofibroblasts are not consistently present in primary keloid lesions.
  • The number and αSMA expression of detected αSMA-positive cells in keloids are comparable to normal and hypertrophic scars.
  • Keloid scars do not appear to depend on αSMA-positive myofibroblasts.

Conclusions:

  • The assumption that αSMA-positive myofibroblasts drive keloid formation is not supported by evidence.
  • Rethinking keloids beyond a spectrum of αSMA expression is crucial for advancing keloid research and treatment development.