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

Lookup NU author(s): Rachel Wilson, Afsara Ahmmed, Dr Alistair Poll, Dr Moto Sakaue, Dr Alex Laude, Professor Maya Sieber-Blum

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 Wilson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.


Publication metadata

Author(s): Wilson R, Ahmmed AA, Poll A, Sakaue M, Laude A, Sieber-Blum M

Publication type: Article

Publication status: Published

Journal: PLoS ONE

Year: 2018

Volume: 13

Issue: 6

Online publication date: 28/06/2018

Acceptance date: 17/06/2018

Date deposited: 10/07/2018

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.pone.0199996

DOI: 10.1371/journal.pone.0199996


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