Scientific poster
Evaluation of local inflammatory reactions following subcutaneous injection of a pro-inflammatory cocktail in a fully human ex vivo skin model. Poster IID2018.
Subcutaneous (SC) injections can evoke local reactions such as inflammation or necrosis.
Preclinical development of SC therapies relies on animal models to characterize these responses, however, translation of these models to the clinic is often limited and no single model has emerged as an accepted standard. Furthermore, animal testing is expensive, time consuming and poses ethical issues. There are currently no in vitro human models to test toxicological effects of SC injections. We developed a new ex vivo human skin model called HypoSkin, containing all skin layers including epidermis, dermis and hypodermis. The skin explant is embedded in a proprietary gel-like matrix with epidermal surface left in direct contact with air. The system is mounted into cell culture inserts and cultured in standard cell culture conditions. Histological analysis of the HypoSkin model showed preserved tissue integrity and cell viability in all 3 skin layers for up to 5 days culture. Distribution of adipocyte sizes across the tissue and total number of adipocytes was also similar before and after ex vivo culture. We demonstrated the feasibility to perform SC injections in the model. Administration of a pro-inflammatory cocktail composed of TNFα and LPS induced after 24 hours dermal collagen degradation and mild cell vacuolization in the epidermis. Increased synthesis of pro-inflammatory cytokines such as IL-6 and IL-8 was also observed and RNAscope analysis revealed strong expression of genes encoding for those cytokines in leucocytes, fibroblasts, adipocytes and endothelial cells of the hypodermis. In conclusion, we have developed a unique fully human ex vivo skin model that allows for SC injection. Moreover, we showed the relevance of this model to respond to injection site inflammatory reactions, demonstrating potential utility of this model to support therapeutic development.
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