Modeling Human Hypertrophic Scars with Induced Pluripotent Stem-Cell-Derived Scar Organoids Versus Skin Organoids

Area of Science:

• Regenerative Medicine
• Dermatology
• Stem Cell Biology

Background:

• Hypertrophic scars involve excessive collagen, fibrosis, and impaired function.
• Current models struggle to accurately replicate human hypertrophic scar pathology.
• Induced pluripotent stem cells (iPSCs) offer a potential source for disease modeling.

Purpose of the Study:

• To develop and characterize a novel in vitro model of hypertrophic scars using iPSC-derived organoids.
• To investigate the key pathological features of hypertrophic scars in a controlled experimental system.
• To establish a platform for future drug screening and mechanistic studies of scar formation.

Main Methods:

• Human iPSCs were differentiated into skin organoids.
• Fibrotic transformation was induced using TGF-β1 and hypoxia.
• Scar organoids were analyzed for collagen deposition, morphology, and gene expression via immunofluorescence and RNA sequencing.

Main Results:

• Scar organoids exhibited significant contraction and increased collagen I deposition compared to skin organoids.
• Reduced LHX2 expression indicated a loss of hair follicle development.
• Distinct transcriptomic profiles revealed altered expression of hair follicle and epidermal genes.

Conclusions:

• iPSC-derived scar organoids successfully recapitulate key hypertrophic scar features in vitro.
• This model demonstrates excessive collagen production, loss of skin appendages, and contractile behavior.
• The platform holds potential for drug screening, precision medicine, and understanding scar pathogenesis.