Neural crest-derived mesenchymal stem cells: Fates and perspectives

Abstract

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.

Keywords: Neural crest; Mesenchymal stem cell; Development; Pluripotent stem cell; Clinical trials

Core Tip: Recent studies have revealed the distribution and functions of neural crest (NC)-derived mesenchymal stem cells (MSCs) in various tissues, with regenerative therapies based on these cells showing positive results in research and clinical practice. Future research focuses on optimizing therapeutic strategies (timing, dosage), expanding clinical applications, and addressing current challenges. Several approaches aim to solve issues like insufficient cell numbers, heterogeneity, and trauma. Notably, MSCs differentiated from pluripotent stem cells via NC pathways show promise as a stable NC-derived MSC source, potentially overcoming current limitations in clinical applications.