Human peptidergic nociceptive sensory neurons generated from human epidermal neural crest stem cells (hEPI-NCSC)

• Published in: PloS one Vol. 13; no. 6; p. e0199996
• Main Authors: Wilson, Rachel, Ahmmed, Afsara A, Poll, Alistair, Sakaue, Motoharu, Laude, Alex, Sieber-Blum, Maya
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.06.2018; Public Library of Science (PLoS)
• Subjects: Analgesics; Arthritis; Biology and Life Sciences; Brn-3 protein; Calcitonin; Calcitonin gene-related peptide; Capsaicin; Capsaicin receptors; Cell Differentiation; Developmental biology; Diabetes; Diabetic neuropathy; Differentiation; Disease; Disease control; Drug discovery; Embryogenesis; Embryonic growth stage; Fibroblasts; Follicles; Gene expression; Gene Expression Regulation; Genes; Growth factors; Humans; Molecular chains; Multipotent Stem Cells - cytology; Multipotent Stem Cells - metabolism; Neural crest; Neural Crest - cytology; Neural Crest - metabolism; Neurogenesis; Neurons; Neuropeptides; New technology; Nociception; Nociceptors - cytology; Nociceptors - metabolism; Pain; Pain perception; Physiological aspects; Proteins; Research and Analysis Methods; Sensory neurons; Sensory properties; Sensory receptors; Signal Transduction; Sox10 protein; Stem cell research; Stem cells; Substance P; Veterinary medicine; United Kingdom > UK
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0199996

Here we provide new technology for generating human peptidergic nociceptive sensory neurons in a straightforward and efficient way. The cellular source, human epidermal neural crest stem cells (hEPI-NCSC), consists of multipotent somatic stem cells that reside in the bulge of hair follicles. hEPI-NCSC and primary sensory neurons have a common origin, the embryonic neural crest. For directed differentiation, hEPI-NCSC were exposed to pertinent growth factors and small molecules in order to modulate master signalling networks involved in differentiation of neural crest cells into postmitotic peptidergic sensory neurons during embryonic development. The neuronal populations were homogenous in regard to antibody marker expression. Cells were immunoreactive for essential master regulatory genes, including NGN1/2, SOX10, and BRN3a among others, and for the pain-mediating genes substance P (SP), calcitonin gene related protein (CGRP) and the TRPV1 channel. Approximately 30% of total cells responded to capsaicin, indicating that they expressed an active TRPV1 channel. In summary, hEPI-NCSC are a biologically relevant and easily available source of somatic stem cells for generating human peptidergic nociceptive neurons without the need for genetic manipulation and cell purification. As no analgesics exist that specifically target TRPV1, a ready supply of high-quality human peptidergic nociceptive sensory neurons could open the way for new approaches, in a biologically relevant cellular context, to drug discovery and patient-specific disease modelling that is aimed at pain control, and as such is highly desirable.