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Caspase inhibition increases survival of neural stem cells in the gastrointestinal tract
Author(s) -
Micci M.a .,
Pattillo M. T .,
Kahrig K. M .,
Pasricha P. J .
Publication year - 2005
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2005.00702.x
Subject(s) - immunosuppression , apoptosis , transplantation , gastrointestinal tract , neural stem cell , biology , stem cell , enteric nervous system , caspase 3 , caspase , immunology , immune system , cancer research , pharmacology , programmed cell death , medicine , microbiology and biotechnology , endocrinology , biochemistry
Neural stem cell (NSC) transplantation is a promising tool for the restoration of the enteric nervous system in a variety of motility disorders. Post‐transplant 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.