Neural crest-derived mesenchymal stem cells: Fates and perspectives

Neural crest-derived mesenchymal stem cells (NC-MSCs) represent a unique population with remarkable regenerative potential, owing to their embryonic origin and exceptional differentiation capacity. These cells demonstrate superior performance in neural and craniofacial tissue regeneration compared to conventional mesenchymal stem cells, with dental stem cells emerging as particularly promising candidates for clinical applications in periodontics and endodontics. Despite their therapeutic promise, adult NC-MSCs face significant challenges including donor site limitations, cellular heterogeneity, and scalability issues. Recent advances in pluripotent stem cell offer potential solutions through the generation of NC-MSCs in vitro, though safety concerns regarding tumorigenicity and long-term stability remain to be addressed through comprehensive preclinical studies. This review provides a comprehensive analysis of NC-MSC biology, highlighting their developmental origins, molecular characteristics, and current applications in regenerative medicine. We critically evaluate existing challenges and future directions, emphasizing the need for standardized protocols, improved characterization methods, and rigorous preclinical evaluation to facilitate clinical translation and therapeutic implementation.