*FRANÇOIS BERTHOD

Innervated, Vascularised and Immunocompetent Human Skin Model for Screening the Sensitization Potential of Chemicals

Challenge: One of the major concerns in the development of a new compound by the chemical, pharmaceutical or cosmetic industries is to assess its ability to induce cutaneous allergic reactions. Indeed, the industry must be able to predict such risk and classify it before commercialization of new molecules. To date, these tests are performed on animals, raising issues of both ethics and reliability. In addition, there are few reliable models of engineered skin that can augment the development on new therapeutic candidates.

Solution: The goal of this project was to develop an innovative immunocompetent tissue-engineered skin model, combining dendritic cells (DCs) (the major immune cells of the dermis), sensory neurons and a capillary network. The main advantage of this model is the coculture of cells in a 3D environment that closely mimics the in vivo environment, allowing physiological interactions between epidermis, neurons, capillaries and DCs. The team demonstrated that stimulation of nerves with capsaicin induced the release of TNFα. This result highlighted the importance of the crosstalk between neurons and innate immune activation and suggested that the proinflammatory properties of a compound is in part related to the involvement of neurons, as shown in mice treated with imiquimod.

Achievements/Impact: A novel engineered skin model was established and validated. This platform represents a useful screening approach for pharmaceutical or chemical industries to assess the potential deleterious cutaneous effects of any new molecule in development. In addition, the model could be used to interrogate skin biology, identify disease targets and screen for new therapeutic drugs for the treatment of skin diseases or wound healing.

Principal Investigator:

François Berthod
Université Laval / CHU de Québec

Co-investigator

Vincent Flacher
CNRS (France)

Completed Project
$1,535,000 / 3 years
Supported by CQDM through:
• Merck
• Pfizer
• MESI
• BL-NCE
And by co-funding partners:
• Alsace BioValley (France)
• Lyonbiopôle (France)