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Publication : Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon.

First Author  McCann CJ Year  2017
Journal  Nat Commun Volume  8
Pages  15937 PubMed ID  28671186
Mgi Jnum  J:250231 Mgi Id  MGI:5920601
Doi  10.1038/ncomms15937 Citation  McCann CJ, et al. (2017) Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon. Nat Commun 8:15937
abstractText  Enteric nervous system neuropathy causes a wide range of severe gut motility disorders. Cell replacement of lost neurons using enteric neural stem cells (ENSC) is a possible therapy for these life-limiting disorders. Here we show rescue of gut motility after ENSC transplantation in a mouse model of human enteric neuropathy, the neuronal nitric oxide synthase (nNOS-/-) deficient mouse model, which displays slow transit in the colon. We further show that transplantation of ENSC into the colon rescues impaired colonic motility with formation of extensive networks of transplanted cells, including the development of nNOS+ neurons and subsequent restoration of nitrergic responses. Moreover, post-transplantation non-cell-autonomous mechanisms restore the numbers of interstitial cells of Cajal that are reduced in the nNOS-/- colon. These results provide the first direct evidence that ENSC transplantation can modulate the enteric neuromuscular syncytium to restore function, at the organ level, in a dysmotile gastrointestinal disease model.
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