Sensory Reinnervation of Human Skin by Human Neural Stem Cell-Derived Peripheral Neurons Ex Vivo

The study investigated the ability of human induced pluripotent stem cell-derived neural stem cells (nSCs) to differentiate into sensory neurons and reinnervate human skin ex vivo. The nSCs successfully differentiated into peripheral neurons and reinnervated the skin when cocultured with human skin punches for 10-12 days. The new nerve fibers were found around hair follicles and in the epidermis, innervating structures and cells in the skin, including hair follicles, mast cells, and blood vessels. The reinnervated skin showed increased survival of mast cells, higher blood vessel density, and increased epidermal proliferation compared to noninnervated controls. This suggests that sensory reinnervation improves these aspects in organ-cultured human skin, highlighting the importance of sensory innervation in human skin. The findings provide new opportunities for preclinical research into the communication between primary human sensory nerve fibers and defined skin cell populations in native human skin.