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

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.

On the road again: Establishment and maintenance of stemness in the neural crest from embryo to adulthood

“…216,217 Although lineage tracing studies using P0 and/or Wnt1-cre recombination in mice have identified the NC origin of some of these neonatal and adult stem cell populations and/or the expression of common NC markers, 10,201,205,209,210 the mechanisms that maintain their stemness and the physiological roles of these cells are poorly understood. The NC-derived stem cells isolated from neonatal or adult tissues maintain high stem cell potency and can be differentiated into several of the NC derivatives such as neurons, glia, smooth muscle cells, melanocytes, bone cells, fibroblasts, and chondrocytes in vitro (reviewed in detail elsewhere 218,219 The discovery of NC-derived stem cells in skin has been particularly exciting considering this could be an easily accessible source of the cells for autologous transplantation for treatment of disease conditions. Since this discovery, several studies have isolated NC-derived progenitor or stem cells from human skin.…”

Stem Cells Regenerating the Craniofacial Skeleton: Current State-Of-The-Art and Future Directions

“…Within dental tissues, there are five main classes of MSC populations, including (I) dental pulp stem cells (DPSCs), (II) stem cells from exfoliated deciduous teeth (SHEDs), (III) periodontal ligament stem cells (PDLSCs), (IV) dental follicle progenitor stem cells (DFPSCs), and (V) stem cells from apical papilla (SCAPs) [ 26 ]. Beyond the five main classes, neural crest stem cells have also emerged as a prominent cell population arising in the dorsal neural tube that give rise to a diverse array of cell types in the body, including craniofacial cartilage and bone [ 27 ]. The most easily extracted and isolated of the aforementioned odontogenic cell lines are the SHEDs, commonly isolated through minimally invasive approaches.…”

Schwann cells: Rescuers of central demyelination

“…So far non-myelinating and myelinating Schwann cells participate to CNS repair. Stem cells are also present in the adult PNS and namely in the adult DRG (reviewed in (Mehrotra, Tseropoulos, Bronner, & Andreadis, 2019)). Yet their activation and involvement in response to CNS injury remains to be addressed.…”