It is known that the main bioenergetic pathway in skin is the anaerobic glycolysis. Thus, glucose consumption and a high production of lactate are a proof of an active metabolism in skin. This has never been demonstrated in an ex vivo human skin model before.
NativeSkin® is an ex vivo human skin model, composed of the two upper skin layers. The skin explant is embedded in a proprietary gel-like matrix with epidermal surface left in direct contact with the air. The system is mounted into cell culture inserts and maintained in standard cell culture conditions. This model represents a highly predictive and cost-effective last-line screening tool in laboratory conditions prior to in vivo clinical evaluations.
Histological analysis of the NativeSkin® model showed preserved tissue integrity for up to 10 days of culture. WST-8 assays showed a cell viability of about 64% after ex vivo culture compared to skin just after surgery. Cell proliferation and apoptosis were quantified in the epidermis. Ki67 was still expressed (3,9% of positive nuclei after 10 days compared to 10% at Day 0), and a low level of active Caspase 3 was visible.
Dosing of two main metabolites, glucose and lactate, were performed on both culture media and skin biopsies after 10 and 20 days of culture. Results showed active metabolism in the NativeSkin® model still after 10 days of culture, with an important glucose consumption (58% of fresh medium glucose consumed) in parallel of a high production of lactate.
In conclusion, we demonstrated the feasibility to maintain skin biopsies alive for up to 10 days, with a preserved tissue integrity, a good cell viability and proliferation, and active metabolism. These results, taken with results previously published on NativeSkin® models, underly that NativeSkin® is a relevant model to study drug penetration and metabolization after repeated topical application during 10 days.

Preservation of human skin integrity and metabolism during 10 days in culture with NativeSkin® system