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Transplanted progenitors generate functional enteric neurons in the postnatal colon
Ryo Hotta, … , John B. Furness, Heather M. Young
Ryo Hotta, … , John B. Furness, Heather M. Young
Published February 1, 2013
Citation Information: J Clin Invest. 2013;123(3):1182-1191. https://doi.org/10.1172/JCI65963.
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Research Article Gastroenterology Article has an altmetric score of 17

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 6

Morphology and electrophysiological properties of graft-derived neurons.

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Morphology and electrophysiological properties of graft-derived neurons....
(A–F) Impaled graft-derived neuron 3 weeks after transplantation of a fNS. (A) Low-magnification image showing a biocytin-filled neuron, which had a single long, circumferentially projecting, axon-like process (yellow arrow) that projected for about 0.6 mm in the plane of the myenteric plexus and finished in an expansion bulb, where the process had broken off during tissue preparation. (B) High-magnification image of the neuron in A, showing multiple filamentous (open arrows) and lamellar (filled arrows) dendrite-like processes. (C and D) Single optical section through neuron in A (asterisk), confirming that it expressed KikGR (D) and hence was graft-derived. (E) The neuron fired a single AP at the beginning of a 500-ms depolarizing step current. (F) fEPSPs occurred both spontaneously (open arrows) and were evoked by a single-pulse stimulus (0.6 mA; filled arrow). Membrane potential was held at –82 mV. (G–K) Impaled graft-derived neuron 4 weeks after transplantation of a pNS. (G) The neuron had lamellar dendrite-like processes (white arrows) and a single long, axon-like process (yellow arrow). (H and I) Single optical section through the neuron in G (asterisk), confirming that it expressed KikGR (I). (J) The neuron fired 3 single APs at the beginning of a 500-ms depolarizing step current. (K) A fEPSP was evoked by a single-pulse stimulus (1.4 mA; arrow). Membrane potential was held at –100 mV. Scale bars: 50 μm (A); 10 μm (B–D and G–I).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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