Context of Use or Disease: Skin senescence and ageing

DOI: Genome Medicine 2025

Platform: Transwell

Description: 3D living skin equivalent containing dermal and epidermal compartments using primary, non-immortalised human cells. Dermal fibroblasts are suspended in a collagen I/Matrigel matrix within a Transwell to form a dermal gel. 24 hours later, keratinocytes are layered on top and raised to the air/liquid interface. The inclusion of a physiologically relevant level of senescent fibroblasts within the dermal compartment enables the impact on non-senescent fibroblasts and cells within the epidermis to be investigated. The model acts as a platform for senotherapeutic compound screening for healthspan, as well as isolation of cells for high-throughput single cell omics, supporting mechanistic discovery. 

Fig. 1. Schematic of 3D model and integrated pipelines for drug discovery programmes and mechanistic studies.

Characterisation & Validation: Validation of epidermal stratification using a panel of markers suitable for multiplex microscopy. Inclusion of senescent fibroblasts leads to features of ageing within the epidermis (e.g. epidermal thinning) within a 14-day assay. The model has been used to develop machine learning pipelines for scRNAseq to improve detection of senescent cells in vivo, supporting efforts to identify senotherapeutic vulnerabilities.

Ongoing Research: Multiplex microscopy studies to uncover senescent cell heterogeneity at the single cell level, mechanisms of paracrine senescence in 3D-relevant contexts, senolytic and senostatic drug discovery, inclusion of endothelial and immune cells

Research Team: Cleo Bishop

Lead Contact: Cleo Bishop

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