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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 3

New neurons are generated in vivo after transplantation of enteric NSs into the colon of postnatal mice.

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New neurons are generated in vivo after transplantation of enteric NSs i...
EdU was injected into recipient wild-type mice immediately after transplantation of fNSs or pNSs derived from EdnrbKik mice into the distal colon. 4 weeks later, recipient mice were killed, and the colon was processed to reveal EdU incorporation and Hu immunoreactivity (to identify neurons). Single optical sections show graft-derived Hu+ cells that had incorporated EdU (arrows) after transplantation of fNSs (A–C) or pNSs (D–F). Scale bars: 25 μm.

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

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