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Updated: Sep 14, 2025

Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
Published on: July 28, 2023
Keratin-Mediated Selective Inhibition in Proliferation and Selective Apoptosis of Keloid Fibroblasts
Hyeon Jeong Kang1, Woo Gyeong Kim2, Seong Yeong An2
1Department of Maxillofacial Biomedical Engineering, College of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea.
Abstract:
Keloids are pathological scars characterized by excessive proliferation of fibroblasts and abnormal extracellular matrix (ECM) accumulation, largely mediated by transforming growth factor-β1 (TGF-β1). Current therapeutic approaches often fail due to high recurrence and limited selectivity. Here, we investigate the potential of human hair-derived keratin (HK) as a biomaterial with selective anti-fibrotic activity. Using multiple in vitro models including 2D monolayers, 3D spheroids, fibroblast-keratinocyte coculture, and collagen gel contraction, we evaluated the effects of 0.5% HK on keloid fibroblasts (KFs) and normal dermal fibroblasts (DFs), with and without TGF-β1 stimulation. HK selectively inhibited KF proliferation, viability, and migration while sparing DF. In 3D models, HK significantly reduced KF-mediated spheroid expansion and collagen matrix contraction, even under profibrotic stimulation. Mechanistically, HK activated intrinsic apoptotic signaling, up-regulating pro-apoptotic proteins (Bax, caspase-3, CYCS) and down-regulating Bcl-2 and XIAP. Transcriptomic profiling revealed that HK down-regulated pathways associated with ECM-receptor interaction, focal adhesion, and aminoacyl-tRNA biosynthesis in KF, suggesting a dual modulation of fibrotic remodeling and mitochondrial function. These findings demonstrate that HK exerts selective anti-fibrotic and pro-apoptotic effects on pathological fibroblasts, with minimal impact on normal cells. By modulating both ECM organization and cell survival pathways, keratin demonstrates strong potential as a therapeutic biomaterial for targeted keloid treatment.
Insights
Human hair keratin (HK) selectively targets keloid fibroblasts, inhibiting their growth and reducing scar tissue formation. This biomaterial shows promise for treating keloids with minimal impact on healthy skin cells.
Area of Science:
- Biomaterials Science
- Dermatology
- Wound Healing
Background:
- Keloids are pathological scars resulting from excessive fibroblast activity and extracellular matrix (ECM) deposition, often driven by transforming growth factor-β1 (TGF-β1).
- Existing keloid treatments have limited efficacy and selectivity, leading to high recurrence rates.
- There is a need for novel therapeutic biomaterials that can selectively target scar-forming cells.
Purpose of the Study:
- To investigate the potential of human hair-derived keratin (HK) as a selective anti-fibrotic agent for keloid treatment.
- To evaluate the effects of HK on keloid fibroblasts (KFs) versus normal dermal fibroblasts (DFs) in various in vitro models.
- To elucidate the underlying mechanisms of HK's anti-fibrotic and pro-apoptotic actions.
Main Methods:
- Utilized 2D monolayers, 3D spheroids, co-culture models, and collagen gel contraction assays.
- Assessed the impact of 0.5% HK on KF and DF proliferation, viability, migration, and ECM production.
- Analyzed apoptotic signaling pathways and performed transcriptomic profiling to identify molecular targets.
Main Results:
- HK selectively inhibited KF proliferation, viability, and migration while sparing DFs.
- In 3D models, HK significantly reduced KF-driven spheroid expansion and collagen matrix contraction, even under TGF-β1 stimulation.
- HK induced apoptosis in KFs by up-regulating pro-apoptotic proteins (Bax, caspase-3, CYCS) and down-regulating anti-apoptotic proteins (Bcl-2, XIAP).
- Transcriptomic analysis revealed HK's modulation of ECM-receptor interaction, focal adhesion, and aminoacyl-tRNA biosynthesis pathways in KFs.
Conclusions:
- Human hair keratin (HK) demonstrates selective anti-fibrotic and pro-apoptotic effects on pathological keloid fibroblasts.
- HK modulates key pathways involved in fibrotic remodeling and cellular survival, offering a targeted approach to keloid treatment.
- Keratin holds significant potential as a therapeutic biomaterial for managing keloid scarring.
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