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Updated: Nov 6, 2025

Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
Published on: July 28, 2023
Keloid tissue analysis discredits a role for myofibroblasts in disease pathogenesis
1Centre for Inflammation Biology & Cancer Immunology, Department of Inflammation Biology, School of Immunology & Microbial Sciences, King's College London, London, UK.
Abstract:
Myofibroblasts, renowned for their contractility and extracellular matrix production, are widely considered the key effector cells for nearly all scars resulting from tissue repair processes, ranging from normal scars to extreme fibrosis. For example, it is often assumed that myofibroblasts underpin the characteristics of keloid scars, which are debilitating pathological skin scars lacking effective treatments because of a poor understanding of the disease mechanisms. Here, we present primary and published transcriptional and histological evidence that myofibroblasts are not consistently present in primary keloid lesions, and when alpha-smooth muscle actin (αSMA)-positive cells are detected, they are not greater in number or expressing more αSMA than in normal or hypertrophic scars. In conclusion, keloid scars do not appear to require αSMA-positive myofibroblasts; continuing to consider keloids on a quantitative spectrum with normal or hypertrophic scars, with αSMA serving as a biomarker of disease severity, is hindering advancement of understanding and therapy development.
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.
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