Preclinical assessments: adressing the intricate brain-skin connection via ZOOM#32

The skin is densely innervated by a complex network of nerve fibers responsible for detecting a wide range of environmental stimuli and relaying this information to the brain playing a crucial role in skin health. Additionally sensory neurons are active cells able to bidirectionally interact with other skin cells impacting a variety of biological phenomenon (e.i. ageing, wound healing, itch, inflammation and pigmentation) and are deeply involved in conditions such as atopic dermatitis, eczema, psoriasis, and sensitive skin. Consequently, the cosmetic industry is increasingly exploring the intersection of neuroscience and dermatology to develop innovative products that address the intricate brain-skin connection. A critical tool driving this innovation is the development of in-vitro skin models that incorporate neurons allowing to evaluate compound action on the complex sensory neurons/skin cells crosstalk.

Current models provide versatile platform for compound screening and testing finished cosmetic products. In-vitro assays targeting neurons can go from cost-effective human iPSC-derived neural progenitor cells monolayers to advanced systems like co-cultured reconstructed epidermis, microfluidic chambers, and organs-on-chip models.

One significant advancement in this field was the disruptive technology to create induced pluripotent stem cells (iPSCs) allowing to obtain human sensory neurons derived from human iPSCs. Depending on the culture conditions, human iPSCs can be differentiated into various neuron-like cells sharing characteristics with sensory neurons such as nocireceptors, mechanoreceptors and proprioceptors.

While there is still a limited number of innervated neuron-containing human skin equivalents (HES), some models have successfully been used to determine the neurosensorial effects of therapeutics and cosmetic products/ingredients. Thus, active ingredients have been considered to have positive effects when they could reduce the temperature-, histamine- or capsaicin-induced activation of innervated HES. Such systems have also been used to test the soothing effects of active ingredients on sensitive skin and to evaluate their impact on altered skin models, such as those simulating atopic dermatitis. Additionally, compartmentalized microfluidic devices and organ-on-chip technologies now enable more precise studies, by better mimicking the anatomical distance and microenvironment between, on one side, neuronal cell bodies and, on the other side, axonal endings and skin cells by culturing them in independent compartments. This allows to more precisely measure the effects of an stimuli applied to neurons on skin cells, or vice versa. By integrating neuroscience and cutting-edge in-vitro techniques, the cosmetic industry is transforming preclinical research and unlocking new opportunities to harness the brain-skin connection.