Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease

E-ISSN： 1365-2982|1350-1925|10|1509-1514

ISSN： 1350-1925

Source： NEUROGASTROENTEROLOGY & MOTILITY (ELECTRONIC), Vol.1350-1925, Iss.10, 2015-10, pp. : 1509-1514

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Abstract

AbstractBackgroundTransplantation of enteric neural stem cells (ENSC) holds promise as a potential therapy for enteric neuropathies, including Hirschsprung disease. Delivery of transplantable cells via laparotomy has been described, but we propose a novel, minimally invasive endoscopic method of cell delivery.MethodsEnteric neural stem cells for transplantation were cultured from dissociated gut of postnatal donor mice. Twelve recipient mice, including Ednrb−/− mice with distal colonic aganglionosis, underwent colonoscopic injection of ENSC under direct vision using a 30‐gauge Hamilton needle passed through a rigid cystoureteroscope. Cell engraftment, survival, and neuroglial differentiation were studied 1–4 weeks after the procedure.Key ResultsAll recipient mice tolerated the procedure without complications and survived to sacrifice. Transplanted cells were found within the colonic wall in 9 of 12 recipient mice with differentiation into enteric neurons and glia.Conclusions & InferencesEndoscopic injection of ENSC is a safe and reliable method for cell delivery, and can be used to deliver a large number of cells to a specific area of disease. This minimally invasive endoscopic approach may prove beneficial to future human applications of cell therapy for neurointestinal disease.