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Is the adult mouse striatum a hostile host for neural transplant survival?

Roberton, Victoria H., Evans, Amy E., Harrison, David John, Precious, Sophie Victoria, Dunnett, Stephen Bruce ORCID:, Kelly, Claire and Rosser, Anne Elizabeth ORCID: 2013. Is the adult mouse striatum a hostile host for neural transplant survival? NeuroReport 24 (18) , pp. 1010-1015. 10.1097/WNR.0000000000000066

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Human donor cells, including neurally directed embryonic stem cells and induced pluripotent stem cells with the potential to be used for neural transplantation in a range of neurodegenerative disorders, must first be tested preclinically in rodent models of disease to demonstrate safety and efficacy. One strategy for circumventing the rejection of xenotransplanted human cells is to desensitize the host animal to human cells in the early neonatal period so that a subsequent transplant in adulthood is not immunorejected. This method has been robustly validated in the rat, but currently not in the mouse in which most transgenic models of neurodegeneration have been generated. Thus, we set out to determine whether this could be achieved through modification of the existing rat protocol. Mice were inoculated in the neonatal period with a suspension of human embryonic cortical tissue of varying cell numbers, and received a subsequent human embryonic cortical tissue cell transplant in adulthood. Graft survival was compared with those in mice immunosuppressed with cyclosporine A and those receiving allografts of mouse whole ganglionic eminence tissue. Poor survival was found across all groups, suggesting a general problem with the use of mouse hosts for testing human donor cells.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: allograft, desensitization, human, immunosuppression, mouse, neurodegeneration, rejection, transplantation, xenograft
Publisher: Lippincott, Williams & Wilkins
ISSN: 0959-4965
Funders: Wellcome Trust, MRC, Welsh Government
Date of First Compliant Deposit: 30 March 2016
Last Modified: 12 May 2023 19:06

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