Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease

L. S. Cheng, R. Hotta, H. K. Graham, N. Nagy, A. M. Goldstein, J. Belkind-Gerson

Research output: Contribution to journalArticle

18 Citations (Scopus)

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. We propose a novel, minimally invasive endoscopic method of delivering enteric neuronal stem cells to treat Hirschsprung disease. We show that this method is safe and efficacious in mice with distal colonic aganglionosis.

Original languageEnglish
Pages (from-to)1509-1514
Number of pages6
JournalNeurogastroenterology and Motility
Volume27
Issue number10
DOIs
Publication statusPublished - Oct 1 2015

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Keywords

  • Cell therapy
  • Endoscopy
  • Enteric neural stem cells
  • Enteric neuropathies
  • Hirschsprung disease

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

Cheng, L. S., Hotta, R., Graham, H. K., Nagy, N., Goldstein, A. M., & Belkind-Gerson, J. (2015). Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease. Neurogastroenterology and Motility, 27(10), 1509-1514. https://doi.org/10.1111/nmo.12635