Migration of cells from primary transplants of allo‐ and xenografted foetal striatal tissue in the adult rat brain

Abstract

Primary neural cells derived from human xenografts migrate extensively following transplantation into the adult rat CNS. However, it is unknown whether cells from allografts have the same capability to migrate within the adult rat brain. Moreover, it is unclear whether human-derived cells migrate to this extent as an inherent property of being in a xenograft environment, or whether it is due to the large size of the developed human brain compared with the adult rat brain. In order to address these issues we have designed an experimental paradigm to investigate the potential for cells derived from grafts of primary rat, mouse and human foetal striatal tissue to migrate following intrastriatal transplantation in an adult rat model of Huntington's disease (HD). Green fluorescent protein (GFP)-expressing rat and mouse donors and an antibody specific to human nuclear antigen enabled identification of graft-derived cells within the host brain, and double-labelling with GFP and neuronal nuclear antigen or immunostaining with human-specific tau identified graft-derived neurons. Twelve weeks post-transplantation, cells had migrated throughout the host in all groups; however, human cells and neurons had migrated significantly more than rat or mouse cells. These results demonstrate that neural cells derived from allografts are capable of migrating in the adult rat CNS and that the extent of migration is most likely determined by the size of the mature donor adult brain. This has important implications for the use of allo- and xenogeneic tissue as a source for transplantation in treating diffuse neurodegenerative disorders such as HD.