Communication between the nervous system and melanocytes have long been suspected on the basis of their common embryologic origin and on several forms of clinical evidence. Histological and ultrastructural studies ultimately confirmed these intimate morphological contacts in the normal human skin, which are strikingly exacerbated in the pathophysiology of certain dermatoses and hyperpigmented lesions. To date, no in vitro human model comprises the required features to accurately study these interactions. To build a fully human innervated and pigmented tissue-engineered model, skin equivalents (SEs) were prepared by co-culturing human dermal fibroblasts and microvascular endothelial cells with hiPSC-derived sensory neurons into a unique porous scaffold made of chitosan-cross-linked collagen glycosaminoglycan polymer, subsequently epidermized with keratinocytes and melanocytes. Human Schwann cells were also added during the culture of the dermal equivalent. Histological analysis confirmed that keratinocytes produced a well-organised and terminally differentiated epidermis containing numerous melanocytes homogenously distributed in the basal cell layer. At the dermal level, CD31 and podoplanin immunostaining demonstrated that endothelial blood and lymphatic cells adhered and proliferated to form numerous capillary-like ring structures embedded in the neo-synthetized extracellular matrix (ECM). Neurofilaments network from iPSC-derived sensory neurons seeded at the bottom of the sponge infiltrated the entire native dermal ECM, as shown by the immunodetection of TUJ1. Spanning of neurites network was not only limited to the dermis but was also found within the epidermal compartment in close contact with melanocytes. This advanced fully human innervated 3D skin model integrating seven different cell types including a functional pigmentary system may be a relevant tool to further decipher the interactions between the nervous and pigmentary systems.

ESDR511 - Three-dimensional culture of human sensory neurons derived from iPS cells in a pigmented and endothelialized tissue-engineered reconstructed skin enriched with Schwann cells

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.