Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease.

Abstract

BACKGROUND:

Transplantation 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.

METHODS:

Enteric 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 RESULTS:

All 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 & INFERENCES:

Endoscopic 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.

• Authors: L S Cheng, R Hotta, H K Graham, N Nagy, A M Goldstein, J Belkind-Gerson
• Journal: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (Neurogastroenterol Motil) Vol. 27 Issue 10 Pg. 1509-14 (Oct 2015) ISSN: 1365-2982 [Electronic] England
• PMID: 26190543 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• EDNRB protein, mouse
• Receptor, Endothelin B

Topics

• Animals
• Colonoscopy (methods)
• Disease Models, Animal
• Enteric Nervous System (cytology)
• Hirschsprung Disease (therapy)
• Mice
• Mice, 129 Strain
• Mice, Inbred C57BL
• Mice, Transgenic
• Neural Stem Cells (transplantation)
• Receptor, Endothelin B