12/23/2023 0 Comments Nervous system stampWhen cultured as neurospheres, ENSPC display ENS progenitor cell properties as they proliferate and differentiate to produce both glia and neurons with phenotypes characteristic of ENS neural cells. While some of the transcription factors, receptors, ligands and other cell signalling components necessary for ENS development have been established, the mechanisms determining ENSPC migration/stasis, proliferation/quiescence and differentiation of specific neural phenotypes are not fully understood.ĮNSPC have been isolated from the gut of both embryonic and postnatal rodent embryos, and also from postnatal human bowel. During this migration through the mesenchyme of the gut wall, the cells behave as multipotent progenitor cells (ENSPC) as they proliferate and differentiate into the neurons and glial cells of ENS ganglia. 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 creditedĭata Availability: All relevant data are within the paper.įunding: DJW was supported by a grant RTF/1395 from Action Medical Research UK ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.ĭuring embryonic development, the enteric nervous system (ENS) is mainly derived from cells originating in the vagal region of the neural crest which migrate caudally to colonize the whole length of the gut. Received: NovemAccepted: MaPublished: May 18, 2015Ĭopyright: © 2015 Wilkinson et al. PLoS ONE 10(5):Īcademic Editor: Irina Kerkis, Instituto Butantan, BRAZIL The derivation of enteric nervous system progenitors in the aganglionic gut region of Hirschprung’s patients not only means that this tissue is a potential source of cells for future autologous transplantation, but it also raises the possibility of inducing the differentiation of these endogenous cells in situ to compensate for the aganglionosis.Ĭitation: Wilkinson DJ, Bethell GS, Shukla R, Kenny SE, Edgar DH (2015) Isolation of Enteric Nervous System Progenitor Cells from the Aganglionic Gut of Patients with Hirschsprung’s Disease. To determine the origin of the progenitor cells in aganglionic region, we used fluorescence-activated cell sorting to demonstrate that only p75-positive neural crest-derived cells present in the thickened nerve trunks characteristic of the aganglionic region of Hirschsprung gut gave rise to neurons in culture. Furthermore, expression of the neural markers NOS, VIP and GFAP also increased during culture of aganglionic gut neurospheres which we show can be transplantation into cultured embryonic mouse gut explants to restore a normal frequency of contractility. Although the enteric nervous system marker calretinin is not expressed in the aganglionic gut region, de novo expression is initiated in cultured neurosphere cells isolated from aganglionic Hirschsprung bowel. Here we demonstrate that progenitor cells can also be isolated from aganglionic gut removed during corrective surgery for Hirschsprung’s disease. These progenitor cells may be of future use to treat patients with Hirschprung’s disease, a congenital condition characterized by hindgut dysmotility due to the lack of enteric nervous system ganglia. Enteric nervous system progenitor cells isolated from postnatal human gut and cultured as neurospheres can then be transplanted into aganglionic gut to restore normal patterns of contractility.
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