Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease

Neurogastroenterol Motil. 2015 Oct;27(10):1509-14. doi: 10.1111/nmo.12635. Epub 2015 Jul 17.

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.

Keywords: Hirschsprung disease; cell therapy; endoscopy; enteric neural stem cells; enteric neuropathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • EDNRB protein, mouse
  • Receptor, Endothelin B