Adult tissue–derived neural crest-like stem cells: Sources, regulatory networks, and translational potential

Abstract

Abstract Neural crest (NC) cells are a multipotent stem cell population that give rise to a diverse array of cell types in the body, including peripheral neurons, Schwann cells (SC), craniofacial cartilage and bone, smooth muscle cells, and melanocytes. NC formation and differentiation into specific lineages takes place in response to a set of highly regulated signaling and transcriptional events within the neural plate border. Premigratory NC cells initially are contained within the dorsal neural tube from which they subsequently emigrate, migrating to often distant sites in the periphery. Following their migration and differentiation, some NC-like cells persist in adult tissues in a nascent multipotent state, making them potential candidates for autologous cell therapy. This review discusses the gene regulatory network responsible for NC development and maintenance of multipotency. We summarize the genes and signaling pathways that have been implicated in the differentiation of a postmigratory NC into mature myelinating SC. We elaborate on the signals and transcription factors involved in the acquisition of immature SC fate, axonal sorting of unmyelinated neuronal axons, and finally the path toward mature myelinating SC, which envelope axons within myelin sheaths, facilitating electrical signal propagation. The gene regulatory events guiding development of SC in vivo provides insights into means for differentiating NC-like cells from adult human tissues into functional SC, which have the potential to provide autologous cell sources for the treatment of demyelinating and neurodegenerative disorders. Significance statement Neural crest (NC) cells have attracted attention for their multipotent nature and ease of isolation from adult tissues. This concise review reports the advantages of using NCs for the treatment of demyelinating disorders and spinal cord injury (SCI), over other cell sources such as induced pluripotent stem cells and embryonic stem cells. Adult tissue-derived NCs are easy to expand in vitro and can be derived from autologous sources. Moreover, differentiation of NCs to Schwann cells (SC) can be easily achieved without genetic mutation, making them safe for translation from a laboratory to a clinical setting. Adult NC-derived SC are functional and can myelinate neurons in vitro and spinal cord in vivo in mice. Hence, NCs derived from adult tissue are a promising cell source for the treatment of demyelinating disorders and SCI. Furthermore, this technology can also be used for disease modeling and drug testing, making way for personalized therapeutics for neurological disorders.