Neural crest stem cells and their potential therapeutic applications

• Published in: Developmental biology 2016-11, Vol.419 (2), p.199-216
• Main Authors: Liu, Jessica Aijia, Cheung, Martin
• Format: Article
• Language: English
• Subjects: Adult Stem Cells - transplantation; Animals; Cell Culture Techniques; Cell Lineage; Cells, Cultured - transplantation; Embryonic Development; Epithelial-Mesenchymal Transition; Fetal Tissue Transplantation; Forecasting; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Human embryonic stem cells; Human Embryonic Stem Cells - transplantation; Humans; Induced pluripotent stem cells; Induced Pluripotent Stem Cells - transplantation; Melanocytes; Mesenchymal; Nervous System Diseases - surgery; Neural Crest - physiology; Neural Crest - transplantation; Neural crest stem cells; Neural Stem Cells - transplantation; Neurogenesis; Organ Specificity; Stem Cell Transplantation; Vertebrates - embryology
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2016.09.006

The neural crest (NC) is a remarkable transient structure generated during early vertebrate development. The neural crest progenitors have extensive migratory capacity and multipotency, harboring stem cell-like characteristics such as self-renewal. They can differentiate into a variety of cell types from craniofacial skeletal tissues to the trunk peripheral nervous system (PNS). Multiple regulators such as signaling factors, transcription factors, and migration machinery components are expressed at different stages of NC development. Gain- and loss-of-function studies in various vertebrate species revealed epistatic relationships of these molecules that could be assembled into a gene regulatory network defining the processes of NC induction, specification, migration, and differentiation. These basic developmental studies led to the subsequent establishment and molecular validation of neural crest stem cells (NCSCs) derived by various strategies. We provide here an overview of the isolation and characterization of NCSCs from embryonic, fetal, and adult tissues; the experimental strategies for the derivation of NCSCs from embryonic stem cells, induced pluripotent stem cells, and skin fibroblasts; and recent developments in the use of patient-derived NCSCs for modeling and treating neurocristopathies. We discuss future research on further refinement of the culture conditions required for the differentiation of pluripotent stem cells into axial-specific NC progenitors and their derivatives, developing non-viral approaches for the generation of induced NC cells (NCCs), and using a genomic editing approach to correct genetic mutations in patient-derived NCSCs for transplantation therapy. These future endeavors should facilitate the therapeutic applications of NCSCs in the clinical setting. •A gene regulatory network comprising signaling molecules and transcription factors regulates neural crest development.•Molecular characterization and developmental potency of both embryonic and adult tissues-derived neural crest stem cells are discussed.•Derivation and characterization of neural crest stem cells from pluripotent stem cells and skin fibroblasts are described.•Applications of patient-specific neural crest stem cells for modeling and treating neurocristopathies are described.