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

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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 2005

Fingerprint

Neural Stem Cells
Caspases
Gastrointestinal Tract
Pylorus
Cyclosporine
Transplantation
Apoptosis
Enteric Nervous System
Caspase 1
Stem Cell Transplantation
Immunosuppression
Cell Proliferation
Transplants
Injections
Therapeutics
interleukin-1beta-converting enzyme inhibitor

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology
  • Neuroscience(all)

Cite this

Caspase inhibition increases survival of neural stem cells in the gastrointestinal tract. / Micci, Maria; Pattillo, M. T.; Kahrig, K. M.; Pasricha, Pankaj Jay.

In: Neurogastroenterology and Motility, Vol. 17, No. 4, 08.2005, p. 557-564.

Research output: Contribution to journalArticle

Micci, Maria ; Pattillo, M. T. ; Kahrig, K. M. ; Pasricha, Pankaj Jay. / Caspase inhibition increases survival of neural stem cells in the gastrointestinal tract. In: Neurogastroenterology and Motility. 2005 ; Vol. 17, No. 4. pp. 557-564.
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