{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:37:48Z","timestamp":1790674668762,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,12,20]],"date-time":"2015-12-20T00:00:00Z","timestamp":1450569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004143","name":"Society of University Surgeons Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004143","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK103785"],"award-info":[{"award-number":["R01DK103785"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2016,4]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Transplanting autologous patient\u2010derived enteric neuronal stem\/progenitor cells (\n ENSC<\/jats:styled-content>\n s) is an innovative approach to replacing missing enteric neurons in patients with Hirschsprung disease (\n HSCR<\/jats:styled-content>\n ). Using autologous cells eliminates immunologic and ethical concerns raised by other cell sources. However, whether postnatal aganglionic bowel is permissive for transplanted\n ENSC<\/jats:styled-content>\n s and whether\n ENSC<\/jats:styled-content>\n s from\n HSCR<\/jats:styled-content>\n patients can be successfully isolated, cultured, and transplanted\n in vivo<\/jats:italic>\n remains unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n ENSC<\/jats:styled-content>\n s isolated from the ganglionic intestine of Ednrb\n \u2212\/\u2212<\/jats:sup>\n mice (\n HSCR<\/jats:styled-content>\n \u2010\n ENSC<\/jats:styled-content>\n s) were characterized immunohistochemically and evaluated for their capacity to proliferate and differentiate\n in vitro<\/jats:italic>\n . Fluorescently labeled\n ENSC<\/jats:styled-content>\n s were co\u2010cultured\n ex vivo<\/jats:italic>\n with aganglionic Ednrb\n \u2212\/\u2212<\/jats:sup>\n colon. For\n in vivo<\/jats:italic>\n transplantation,\n HSCR<\/jats:styled-content>\n \u2010\n ENSC<\/jats:styled-content>\n s were labeled with lentivirus expressing green fluorescent protein (\n GFP<\/jats:styled-content>\n ) and implanted into aganglionic embryonic chick gut\n in ovo<\/jats:italic>\n and postnatal aganglionic Ednrb\n \u2212\/\u2212<\/jats:sup>\n rectum\n in vivo<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n HSCR<\/jats:styled-content>\n \u2010\n ENSC<\/jats:styled-content>\n s maintain normal capacity self\u2010renewal and neuronal differentiation. Moreover, the Ednrb\n \u2212\/\u2212<\/jats:sup>\n aganglionic environment is permissive to engraftment by wild\u2010type\n ENSC<\/jats:styled-content>\n s\n ex vivo<\/jats:italic>\n and supports migratrion and neuroglial differentiation of these cells following transplantation\n in vivo<\/jats:italic>\n . Lentiviral\n GFP<\/jats:styled-content>\n \u2010labeled\n HSCR<\/jats:styled-content>\n \u2010\n ENSC<\/jats:styled-content>\n s populated embryonic chick hindgut and postnatal colon of Ednrb\n \u2212\/\u2212<\/jats:sup>\n HSCR<\/jats:styled-content>\n , with cells populating the intermuscular layer and forming enteric neurons and glia.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions & Inferences<\/jats:title>\n \n ENSC<\/jats:styled-content>\n s can be isolated and cultured from mice with\n HSCR<\/jats:styled-content>\n , and transplanted into the aganglionic bowel of\n HSCR<\/jats:styled-content>\n littermates to generate enteric neuronal networks. These results in an isogenic model establish the potential of using autologous\u2010derived stem cells to treat\n HSCR<\/jats:styled-content>\n and other intestinal neuropathies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/nmo.12744","type":"journal-article","created":{"date-parts":[[2015,12,20]],"date-time":"2015-12-20T23:28:48Z","timestamp":1450654128000},"page":"498-512","source":"Crossref","is-referenced-by-count":61,"title":["Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease"],"prefix":"10.1111","volume":"28","author":[{"given":"R.","family":"Hotta","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery Massachusetts General Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. S.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Massachusetts General Hospital Harvard Medical School Boston MA USA"},{"name":"Department of Surgery University of California San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. K.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Massachusetts General Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Massachusetts General Hospital Harvard Medical School Boston MA USA"},{"name":"Department of Pediatric Surgery Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Massachusetts General Hospital Harvard Medical School Boston MA USA"},{"name":"Department of Human Morphology and Developmental Biology Faculty of Medicine Semmelweis University Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Belkind\u2010Gerson","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Massachusetts General Hospital Harvard Medical School Boston MA USA"},{"name":"Pediatric Neurogastroenterology Program Massachusetts General Hospital MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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