title: 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.
  
  
  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
  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.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Cheng
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hotta
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Graham
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Semmelweis University, Budapest, Hungary.
authors.forename: N
authors.initials: N
authors.lastname: Nagy
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Pediatric Neurogastroenterology Program, MassGeneral Hospital for Children, Boston, MA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Goldstein
authors.affiliation: Pediatric Neurogastroenterology Program, MassGeneral Hospital for Children, Boston, MA, USA.|Department of Pediatric Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Belkind-Gerson
mesh_terms: D000818:Animals; D003113:Colonoscopy / Q000379:methods*; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000166:cytology*; D006627:Hirschsprung Disease / Q000628:therapy*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000637:transplantation*; D044023:Receptor, Endothelin B
chemical_list: C000602969:EDNRB protein, mouse; D044023:Receptor, Endothelin B
keywords: Hirschsprung disease; cell therapy; endoscopy; enteric neural stem cells; enteric neuropathies