Evaluation of ES-derived neural progenitors as apotential source for cell replacement therapy in thegut

Valentina Sasselli, Maria Micci, Kristen M. Kahrig, Pankaj Jay Pasricha

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Stem cell-based therapy has recently been explored for the treatment of disorders of theenteric nervous system (ENS). Pluripotent embryonic stem (ES) cells represent an attractivecell source; however, little or no information is currently available on how ES cells willrespond to the gut environment. In this study, we investigated the ability of ES cells torespond to environmental cues derived from the ENS and related tissues, both in vitro and invivo. Methods: Neurospheres were generated from mouse ES cells (ES-NS) and co-cultured withorganotypic preparations of gut tissue consisting of the longitudinal muscle layers with theadherent myenteric plexus (LM-MP). Results: LM-MP co-culture led to a significant increase in the expression of pan-neuronal markers(betaIII-tubulin, PGP 9.5) as well as more specialized markers (peripherin, nNOS) in ES-NS,both at the transcriptional and protein level. The increased expression was not associated withincreased proliferation, thus confirming a true neurogenic effect. LM-MP preparationsexerted also a myogenic effect on ES-NS, although to a lesser extent. After transplantation invivo into the mouse pylorus, grafted ES-NS failed to acquire a distinct phenotype al least 1week following transplantation. Conclusions: This is the first study reporting that the gut explants can induce neuronal differentiation of EScells in vitro and induce the expression of nNOS, a key molecule in gastrointestinal motilityregulation. The inability of ES-NS to adopt a neuronal phenotype after transplantation in thegastrointestinal tract is suggestive of the presence of local inhibitory influences that preventsES-NS differentiation in vivo.

Original languageEnglish (US)
Pages (from-to)81
Number of pages1
JournalBMC Gastroenterology
DOIs
StateAccepted/In press - Jun 26 2012

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Embryonic Stem Cells
Cell- and Tissue-Based Therapy
Transplantation
Peripherins
Phenotype
Myenteric Plexus
Pluripotent Stem Cells
Aptitude
Pylorus
Tubulin
Coculture Techniques
Nervous System Diseases
Cues
Stem Cells
Muscles
Proteins
In Vitro Techniques
Therapeutics

ASJC Scopus subject areas

  • Gastroenterology

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Evaluation of ES-derived neural progenitors as apotential source for cell replacement therapy in thegut. / Sasselli, Valentina; Micci, Maria; Kahrig, Kristen M.; Pasricha, Pankaj Jay.

In: BMC Gastroenterology, 26.06.2012, p. 81.

Research output: Contribution to journalArticle

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