Reconstructed human keloid models show heterogeneity within keloid scars

Area of Science:

• Dermatology and tissue engineering.
• Scar research and regenerative medicine.

Background:

• Keloid scars are characterized by an actively growing periphery and a regressing center.
• Understanding keloid heterogeneity is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the heterogeneity within keloid scars and their pathogenesis.
• To utilize an in vitro keloid scar model to analyze different scar regions.

Main Methods:

• Constructed organotypic 3D skin models using keratinocytes and fibroblasts from normal skin and keloid regions (periphery, center, surrounding normal skin).
• Isolated fibroblasts from superficial-central and deep-central keloid regions.
• Analyzed fibroblast contraction, myofibroblast presence, inflammatory cytokine secretion, and collagen IV gene expression.

Main Results:

• Keloid models demonstrated increased contraction, especially in central regions.
• Myofibroblasts were more abundant in models with deep-central keloid fibroblasts.
• Reduced anti-fibrotic HGF and collagen IV gene expression in deep-central keloid regions.
• No significant differences in inflammatory cytokine secretion between peripheral and central keloid regions.
• Surrounding normal skin exhibited characteristics similar to both normal skin and keloids.

Conclusions:

• Developed a novel in vitro 3D scar model for keloid pathology and therapeutic testing.
• The central keloid region presents a more aggressive phenotype than the periphery.
• Adjacent normal skin shares keloid-specific abnormalities, indicating complex scar development.