Preclinical Evaluation of Rho-Associated Protein Kinase Inhibitors in Keloid Disease Using 2D, 3D, and Ex Vivo Models – Abstract
Zeinab Ghasemishahrestani, Traci A. Wilgus, Nonhlanhla P. Khumalo, Ardeshir Bayat
BACKGROUND
Keloid disease (KD) is a fibroproliferative disorder with unknown pathogenesis and no effective treatment. The lack of an animal model and the limitations of 2D in vitro systems restrict evaluation of antifibrotic therapies. To overcome these challenges we developed a novel 3D spheroid model of keloid fibroblasts (KFs) to assess the activity of the Rho-associated protein kinase (ROCK) inhibitor AMA0825 in comparison with dexamethasone (DEX).
CONCLUSION
This study establishes a robust 3D KF spheroid model as a reliable platform for drug testing in KD. AMA0825 demonstrated potent, dose-dependent antiproliferative activity and reduced fibrotic marker expression at higher concentrations, outperforming DEX in proliferation assays. These findings highlight ROCK inhibition as a promising strategy for KD, with AMA0825 showing potential for further preclinical development, particularly in combination with corticosteroids.
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