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Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue

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Katariina Mähönen¹, Isabel Mogollon², Antti Hassinen²

¹Department of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. katariina.mahonen@hus.fi.

Acta Dermato-Venereologica

|August 3, 2025

Summary

Researchers screened 78 drugs to identify new treatments for localized scleroderma, a fibrotic skin disease. Several drug classes, including tyrosine kinase and transforming growth factor-beta inhibitors, showed antifibrotic effects, suggesting new therapeutic targets.

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Area of Science:

Dermatology
Immunology
Pharmacology

Background:

Localized scleroderma is a rare autoimmune disease causing progressive skin fibrosis.
Myofibroblasts drive fibrosis through collagen production, influenced by transforming growth factor-beta (TGF-β).
Current treatments for skin fibrosis have limited efficacy, necessitating novel therapeutic strategies.

Purpose of the Study:

To identify potential new antifibrotic therapies for localized scleroderma by screening a library of drugs.
To evaluate the antifibrotic effects of tested drugs using markers like alpha-smooth muscle actin and collagen-1 expression.
To investigate the role of TGF-β and androgen receptor pathways in localized scleroderma pathogenesis.

Main Methods:

Screening of 78 drugs on lesional localized scleroderma fibroblasts.
Assessment of antifibrotic effects by measuring alpha-smooth muscle actin and collagen-1 expression.
Analysis of TGF-β1, Smad3, AKT, and androgen receptor expression in lesional skin.

Main Results:

Several drugs, including tyrosine kinase, phosphoinositide-3 kinase, and TGF-β receptor inhibitors, demonstrated antifibrotic activity.
Increased expression of TGF-β1, Smad3, and AKT was observed in lesional localized scleroderma skin.
Androgen receptor antagonists also showed potential antifibrotic effects, correlating with increased androgen receptor expression.

Conclusions:

The transforming growth factor-beta pathway is a validated therapeutic target for localized scleroderma.
Inhibitors of tyrosine kinase, phosphoinositide-3 kinase, and TGF-β receptor pathways represent promising candidates for treating skin fibrosis.
Androgen receptor antagonists may offer an additional therapeutic avenue for localized scleroderma.