Neural stem cells express RET, produce nitric oxide, and survive transplantation in the gastrointestinal tract

Maria Micci, Randall D. Learish, Hui Li, Bincy P. Abraham, Pankaj Jay Pasricha

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Transplantation of neural stem cells (NSC) has been shown to be successful in a variety of experimental models of nongastrointestinal diseases. The aim of this study was to assess the potential of NSC transplantation as a therapeutic strategy for neuronal replacement in disorders of the enteric nervous system. Methods: Central nervous system-derived NSC (CNS-NSC) were obtained from the subventricular zone of rat brain (E17). Expression of RET, GFRα1, and neuronal nitric oxide synthase (nNOS) was assessed by Western blot and immunocytochemistry. Nitric oxide (NO) production was assessed using the NO-sensitive fluorescent indicator DAF-2. CNS-NSC (labeled with CM-Dil) were transplanted into the pylorus of mice and fluorescent double-labeling immunostaining for βIII-tubulin or PGP 9.5 and nNOS was performed at 2, 4, and 8 weeks after transplantation. Results: Our results show that CNS-NSC express both the receptors (RET and GFRα1) for the enteric neurotrophin, GDNF; GDNF, in turn, induces expansion of the RET-expressing CNS-NSC population. Furthermore, CNS-NSC express nNOS and produce NO in vitro. When transplanted into the gut, CNS-NSC differentiate into neurons, continue to express nNOS and survive at least 8 weeks. Conclusions: We conclude that transplantation of CNS-NSC bears promise as a potential cellular replacement strategy for enteric neurons.

Original languageEnglish (US)
Pages (from-to)757-766
Number of pages10
JournalGastroenterology
Volume121
Issue number4
StatePublished - 2001

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Neural Stem Cells
Gastrointestinal Tract
Nitric Oxide
Central Nervous System
Transplantation
Nitric Oxide Synthase Type I
Glial Cell Line-Derived Neurotrophic Factor
Enteric Nervous System
Neurons
Lateral Ventricles
Pylorus
Nerve Growth Factors
Stem Cell Transplantation
Tubulin
Theoretical Models
Western Blotting
Immunohistochemistry
Brain
Population

ASJC Scopus subject areas

  • Gastroenterology

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Neural stem cells express RET, produce nitric oxide, and survive transplantation in the gastrointestinal tract. / Micci, Maria; Learish, Randall D.; Li, Hui; Abraham, Bincy P.; Pasricha, Pankaj Jay.

In: Gastroenterology, Vol. 121, No. 4, 2001, p. 757-766.

Research output: Contribution to journalArticle

Micci, M, Learish, RD, Li, H, Abraham, BP & Pasricha, PJ 2001, 'Neural stem cells express RET, produce nitric oxide, and survive transplantation in the gastrointestinal tract', Gastroenterology, vol. 121, no. 4, pp. 757-766.
Micci, Maria ; Learish, Randall D. ; Li, Hui ; Abraham, Bincy P. ; Pasricha, Pankaj Jay. / Neural stem cells express RET, produce nitric oxide, and survive transplantation in the gastrointestinal tract. In: Gastroenterology. 2001 ; Vol. 121, No. 4. pp. 757-766.
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