title: Postnatal human enteric neuronal progenitors can migrate, differentiate, and proliferate in embryonic and postnatal aganglionic gut environments.
abstract: BACKGROUND
  Enteric neural stem/progenitor cells (ENSCs) offer an innovative approach to treating Hirschsprung disease (HSCR) and other enteric neuropathies. However, postnatal-derived human ENSCs have not been thoroughly characterized and their behavior in the embryonic and postnatal intestinal environment is unknown.
  
  
  METHODS
  ENSCs were isolated from the intestines of 25 patients undergoing bowel resection, including 7 children with HSCR. Neuronal differentiation and proliferation of ENSCs from submucosal and myenteric plexuses from patients with and without HSCR were characterized. ENSC migration and differentiation were studied following transplantation into embryonic chick neural crest, embryonic chick hindgut, and postnatal mouse aganglionic colon.
  
  
  RESULTS
  The proliferative and neurogenic potential of ENSCs from HSCR intestine is equivalent to that of non-HSCR controls. Similarly, no difference was observed between myenteric- and submucosal-derived ENSCs. Postnatal ENSCs transplanted to embryonic neural crest pathways and to aneural hindgut migrate normally and differentiate into appropriate neural crest-derived cell types. ENSCs in postnatal mouse aganglionic colon differentiate into neurons and glia both ex vivo and in vivo.
  
  
  CONCLUSIONS
  ENSCs isolated from the postnatal intestine of patients with and without HSCR can behave like embryonic neural crest-derived cells. These results support the feasibility of cell-based therapy for future treatment of neurointestinal disease.
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Surgery, University of California San Francisco, San Francisco, California.
authors.forename: Lily S
authors.initials: LS
authors.lastname: Cheng
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hotta
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Graham
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jaime
authors.initials: J
authors.lastname: Belkind-Gerson
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Nandor
authors.initials: N
authors.lastname: Nagy
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Allan M
authors.initials: AM
authors.lastname: Goldstein
mesh_terms: D000293:Adolescent; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D005260:Female; D006627:Hirschsprung Disease / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007420:Intestine, Large / Q000294:innervation*; D008297:Male; D008810:Mice, Inbred C57BL; D009197:Myenteric Plexus / Q000473:pathology*; D058953:Neural Stem Cells / Q000473:pathology* / Q000637:transplantation; D055495:Neurogenesis; D018874:Spheroids, Cellular; D055153:Stem Cell Niche; D033581:Stem Cell Transplantation; D013368:Submucous Plexus / Q000473:pathology*; D055815:Young Adult