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Transplanted progenitors generate functional enteric neurons in the postnatal colon
Ryo Hotta, Lincon A. Stamp, Jaime P.P. Foong, Sophie N. McConnell, Annette J. Bergner, Richard B. Anderson, Hideki Enomoto, Donald F. Newgreen, Florian Obermayr, John B. Furness, Heather M. Young
Ryo Hotta, Lincon A. Stamp, Jaime P.P. Foong, Sophie N. McConnell, Annette J. Bergner, Richard B. Anderson, Hideki Enomoto, Donald F. Newgreen, Florian Obermayr, John B. Furness, Heather M. Young
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Research Article Gastroenterology

Transplanted progenitors generate functional enteric neurons in the postnatal colon

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Abstract

Cell therapy has the potential to treat gastrointestinal motility disorders caused by diseases of the enteric nervous system. Many studies have demonstrated that various stem/progenitor cells can give rise to functional neurons in the embryonic gut; however, it is not yet known whether transplanted neural progenitor cells can migrate, proliferate, and generate functional neurons in the postnatal bowel in vivo. We transplanted neurospheres generated from fetal and postnatal intestinal neural crest–derived cells into the colon of postnatal mice. The neurosphere-derived cells migrated, proliferated, and generated neurons and glial cells that formed ganglion-like clusters within the recipient colon. Graft-derived neurons exhibited morphological, neurochemical, and electrophysiological characteristics similar to those of enteric neurons; they received synaptic inputs; and their neurites projected to muscle layers and the enteric ganglia of the recipient mice. These findings show that transplanted enteric neural progenitor cells can generate functional enteric neurons in the postnatal bowel and advances the notion that cell therapy is a promising strategy for enteric neuropathies.

Authors

Ryo Hotta, Lincon A. Stamp, Jaime P.P. Foong, Sophie N. McConnell, Annette J. Bergner, Richard B. Anderson, Hideki Enomoto, Donald F. Newgreen, Florian Obermayr, John B. Furness, Heather M. Young

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Figure 1

Enteric neural crest–derived NSs in vitro and after transplantation into the postnatal colon in vivo.

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Enteric neural crest–derived NSs in vitro and after transplantation into...
(A–D) In vitro characterization of a pNS (derived from the gut of a P4 EdnrbKik mouse). After 2 days of culture on fibronectin, many EdnrbKik-positive cells had emigrated from the NS (A), and most showed immunoreactivity to the neural crest cell marker Sox10 (B and D). A subpopulation of cells (arrows) expressed the neuronal marker Tuj1 (C and D). (E) Composite image of low-magnification views of a whole-mount preparation of distal colon, showing graft-derived cells and fibers 4 weeks after transplantation of 2 fNSs (generated from the gut of E14.5 EdnrbKik mice). There was extensive migration of graft-derived cells away from the original transplantation sites (asterisks). Some of the graft-derived cells formed ganglion-like clusters (arrows). A NS at the same scale as the whole-mount colon preparation is shown in the inset. (F) Area occupied by graft-derived cells (left) and fibers (right) at the indicated times after transplantation of NSs generated from the gut of fetal and postnatal mice into the distal colon. Scale bars: 50 μm (A–D); 1 mm (E).

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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