title: Engraftment of enteric neural progenitor cells into the injured adult brain.
abstract: BACKGROUND
  A major area of unmet need is the development of strategies to restore neuronal network systems and to recover brain function in patients with neurological disease. The use of cell-based therapies remains an attractive approach, but its application has been challenging due to the lack of suitable cell sources, ethical concerns, and immune-mediated tissue rejection. We propose an innovative approach that utilizes gut-derived neural tissue for cell-based therapies following focal or diffuse central nervous system injury.
  
  
  RESULTS
  Enteric neuronal stem and progenitor cells, able to differentiate into neuronal and glial lineages, were isolated from the postnatal enteric nervous system and propagated in vitro. Gut-derived neural progenitors, genetically engineered to express fluorescent proteins, were transplanted into the injured brain of adult mice. Using different models of brain injury in combination with either local or systemic cell delivery, we show that transplanted enteric neuronal progenitor cells survive, proliferate, and differentiate into neuronal and glial lineages in vivo. Moreover, transplanted cells migrate extensively along neuronal pathways and appear to modulate the local microenvironment to stimulate endogenous neurogenesis.
  
  
  CONCLUSIONS
  Our findings suggest that enteric nervous system derived cells represent a potential source for tissue regeneration in the central nervous system. Further studies are needed to validate these findings and to explore whether autologous gut-derived cell transplantation into the injured brain can result in functional neurologic recovery.
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. jbelkindgerson@mgh.harvard.edu.|Pediatric Neurogastroenterology Program, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge St #575, Boston, MA, 02114, USA. jbelkindgerson@mgh.harvard.edu.
authors.forename: Jaime
authors.initials: J
authors.lastname: Belkind-Gerson
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. rhotta@mgh.harvard.edu.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hotta
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. mwhalen@mgh.harvard.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Whalen
authors.affiliation: Department of Neurology, Division of Neuro-Oncology, and Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. nnayyar@partners.org.
authors.forename: Naema
authors.initials: N
authors.lastname: Nayyar
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. nnagy@mgh.harvard.edu.
authors.forename: Nandor
authors.initials: N
authors.lastname: Nagy
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. lscheng@mgh.harvard.edu.
authors.forename: Lily
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. zuckermana@wustl.edu.
authors.forename: Aaron
authors.initials: A
authors.lastname: Zuckerman
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. amgoldstein@mgh.harvard.edu.|Pediatric Neurogastroenterology Program, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge St #575, Boston, MA, 02114, USA. amgoldstein@mgh.harvard.edu.
authors.forename: Allan M
authors.initials: AM
authors.lastname: Goldstein
authors.affiliation: Department of Neurology, Division of Neuro-Oncology, and Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. jdietrich1@partners.org.
authors.forename: Jorg
authors.initials: J
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology* / Q000528:radiation effects / Q000601:surgery; D001930:Brain Injuries / Q000601:surgery / Q000628:therapy; D049109:Cell Proliferation; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D017615:Enteric Nervous System / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology* / Q000637:transplantation; D055495:Neurogenesis; D011833:Radiation Injuries, Experimental / Q000601:surgery / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods*
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