Human Pluripotent Stem Cell-Derived Neural Crest Cells for Tissue Regeneration and Disease Modeling

Abstract

Neural crest cells (NCCs) are a multipotent and migratory cell population in the developing embryo that contribute to the formation of a wide range of tissues. Defects in the development, differentiation and migration of NCCs give rise to a class of syndromes and diseases that are known as neurocristopathies. NCC development has historically been studied in a variety of animal models, including xenopus, chick and mouse. In the recent years, there have been efforts to study NCC development and disease in human specific models, with protocols being established to derive NCCs from human pluripotent stem cells (hPSCs), and to further differentiate these NCCs to neural, mesenchymal and other lineages. These in vitro differentiation platforms are a valuable tool to gain a better understanding of the molecular mechanisms involved in human neural crest development. The use of induced pluripotent stem cells (iPSCs) derived from patients afflicted with neurocristopathies has also enabled the study of defective human NCC development using these in vitro platforms. Here, we review the various in vitro strategies that have been used to derive NCCs from hPSCs and to specify NCCs into cranial, trunk, and vagal subpopulations and their derivatives. We will also discuss the potential applications of these human specific NCC platforms, including the use of iPSCs for disease modeling and the potential of NCCs for future regenerative applications.

Between Fate Choice and Self-Renewal—Heterogeneity of Adult Neural Crest-Derived Stem Cells

“… Schematic view on the role of neural crest stem cells in embryogenesis (A) and adulthood (B) as well as suggested differences between favored fate choices of single NCSCs (C) . (A) Modified from Greiner et al (2019a) and Srinivasan and Toh (2019) , NC, Neural crest; NCSCs, Neural crest-derived stem cells; PNS, Peripheral nervous system. …”

The role of teratogens in neural crest development

“…The use of human induced pluripotent stem cells (hiPSC) derived from patients afflicted with NCPs has also enabled the study of defective human NCC development using these in vitro platform (Menendez, Yatskievych, Antin, & Dalton, ; Mica, Lee, Chambers, Tomishima, & Studer, ; Srinivasan & Toh, ). The advantage of this system is that the use of human cells allows a direct extrapolation of the mechanisms unveiled to human development.…”

Stem Cell Neurodevelopmental Solutions for Restorative Treatments of the Human Trunk and Spine

“…Multipotent NCCs share transcriptomic similarities to PSCs and have an impressive capacity to produce a diverse array of adult cell types such as peripheral sensory and autonomic neurons, Schwann cells, enteric ganglia, bone and cartilage, pigmenting melanocytes, sympathoadrenal cells, smooth muscle, and other cells of the mesenchyme in the trunk and craniofacial anatomic compartments (Srinivasan and Toh, 2019 ). Given the multipotent nature of NCCs, differentiation protocols for generating terminal cell types through NCC intermediates are numerous.…”

“…Continued refinement of protocols for NCCs that are regionally patterned along the rostral-caudal neuraxis will be critical to complex regenerative repair of spinal damage. Damage that extends beyond CNS tissue will also require new bone, cartilage, tendon, peripheral nerves, autonomic neurons, and myelinating Schwann cells (Srinivasan and Toh, 2019 ).…”