3D keloid spheroid model: Development and application for personalized drug response prediction

Area of Science:

• Biomedical Engineering
• Dermatology
• Cell Biology

Background:

• Keloid research is hindered by inadequate in vitro and animal models.
• Endothelial cells play a crucial role in keloid pathogenesis.
• Keloids exhibit significant heterogeneity, necessitating models that capture this complexity.

Purpose of the Study:

• To develop and evaluate a novel 3D in vitro keloid spheroid model.
• To determine the optimal ratio of keloid fibroblasts and endothelial cells for spheroid formation.
• To assess the utility of patient-derived keloid spheroids as a model for disease and drug response.

Main Methods:

• Generation of 3D keloid spheroids using commercial keloid fibroblasts and endothelial cells at varying ratios.
• Optimization of spheroid formation based on viability and gene expression analysis.
• Assessment of patient-derived keloid spheroids for heterogeneity and drug response compared to 2D cultures.

Main Results:

• Spheroids with a higher proportion of endothelial cells demonstrated enhanced viability and propagation.
• Patient-derived keloid spheroids exhibited heterogeneity, mirroring individual clinical presentations.
• An optimal fibroblast to endothelial cell ratio of 4:1 was identified for keloid spheroids.
• Patient-derived spheroids showed more accurate keloidal genetic expression changes than 2D cultures.
• Spheroids displayed differential responses and resistance to keloid drugs based on cell composition.

Conclusions:

• The 3D keloid spheroid model offers a more representative in vitro system for studying keloid pathogenesis.
• This model holds promise for evaluating treatment efficacy and advancing precision medicine for keloids.
• Patient-derived spheroids can provide insights into individual keloid characteristics and drug sensitivities.