Caspase inhibition increases survival of neural stem cells in the gastrointestinal tract

M. A. Micci, M. T. Pattillo, K. M. Kahrig, Pankaj Jay Pasricha

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Neural stem cell (NSC) transplantation is a promising tool for the restoration of the enteric nervous system in a variety of motility disorders. Posttransplant survival represents a critical limiting factor for successful repopulation. The aim of this study was to determine the role of both immunological as well as non-immune-mediated mechanisms on post-transplant survival of NSC in the gut. Mouse CNS-derived NSC (CNS-NSC) were transplanted into the pylorus of recipient mice with and without the addition of a caspase-1 inhibitor (Ac-YVAD-cmk) in the injection media. In a separate experiment, CNS-NSC were transplanted in the pylorus of mice that were immunosuppressed by administration of cyclosporin A (CsA). Apoptosis and proliferation of the implanted cells was assessed 1 and 7 days post-transplantation. Survival was assessed 1 week post-transplantation. The degree of immunoresponse was also measured. The addition of a caspase-1 inhibitor significantly reduced apoptosis, increased proliferation and enhanced survival of CNS-NSC. CsA-treatment did not result in improved survival. Our results indicate that caspase-1 inhibition, but not immunosuppression, improves survival of CNS-NSC in the gut. Pre-treatment with a caspase-1 inhibitor may be a practical method to enhance the ability of transplanted CNS-NSC to survive in their new environment.

Original languageEnglish (US)
Pages (from-to)557-564
Number of pages8
JournalNeurogastroenterology and Motility
Volume17
Issue number4
DOIs
StatePublished - Aug 1 2005

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Keywords

  • Apoptosis
  • Caspase-1 inhibitor
  • Cyclosporin
  • Enteric nervous system
  • Neural stem cells
  • Pylorus

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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