title: Is the adult mouse striatum a hostile host for neural transplant survival?
abstract: 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.
authors.affiliation: aBrain Repair Group, School of Biosciences bSchool of Medicine, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University cSchool of Health Sciences, Cardiff Metropolitan University, Cardiff, UK.
authors.forename: Victoria H
authors.initials: VH
authors.lastname: Roberton
authors.forename: Amy E
authors.initials: AE
authors.lastname: Evans
authors.forename: David J
authors.initials: DJ
authors.lastname: Harrison
authors.forename: Sophie V
authors.initials: SV
authors.lastname: Precious
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Dunnett
authors.forename: Claire M
authors.initials: CM
authors.lastname: Kelly
authors.forename: Anne E
authors.initials: AE
authors.lastname: Rosser
mesh_terms: D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods*; D002540:Cerebral Cortex / Q000601:surgery; D003342:Corpus Striatum / Q000473:pathology / Q000601:surgery*; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods*; D006085:Graft Survival; D006801:Humans; D008297:Male; D051379:Mice; D014183:Transplantation, Heterologous / Q000379:methods*