ATMP-classified, scalable, autologous cell spray for the treatment of skin wounds and assessment of its effects on wound healing clinically and on a molecular level

Abstract

BackgroundAutologous split-thickness skin grafts (STSGs) are the standard of care for closure of deep and large burns. However, perforation and extensive fishnet-like expansion of the grafts to achieve greater area wound coverage can lead to treatment failures or esthetically poor healing outcomes and scarring. The purpose of this study was to validate an autologous advanced therapy medicinal product (ATMP)-compliant skin cell suspension and evaluate its efficacy to promote epithelialization. MethodsCells isolated from a piece of STSG according to ATMP classification requirements were sprayed onto 20 patients during a single operation in a validation study. Comparative evaluation of treatment efficacy was carried out using side-by-side skin graft donor site wounds that were standardized in depth. Firstly, we characterized wound healing transcriptomes at 14 and 21 days from serial wound biopsies in seven patients. Then, side-by-side wounds in four patients were treated with or without the skin cells. The wounds were photographed, clinical outcomes assessed, and the treatment and control wound transcriptomes at 14 days were compared to the untreated wounds' healing transcriptomes. ResultsThe average cell yield after isolation from the STSG was 2.4 × 106 cells/cm2 with 96 % viability. The product contained mainly keratinocytes and their precursors but also other skin cells such as fibroblasts were present. As compared to vehicle-treated donor site wounds, the wounds treated with cells demonstrated improved epithelialization by both direct comparison and machine learning analysis of the transcriptomes. ConclusionsWe showed that rapid and scalable ATMP-classified processing of skin cells is feasible, and application of the skin cells effectively promotes healing and epithelization of donor site wounds.