Survival of Neural Progenitors Allografted into the CNS of Immunocompetent Recipients is Highly Dependent on Transplantation Site

Abstract

Allografts continue to be used in clinical neurotransplantation studies; hence, it is crucial to understand the mechanisms that govern allograft tolerance. We investigated the impact of transplantation site within the brain on graft survival. Mouse [Friend leukemia virus, strain B (FVB)] glial precursors, transfected with luciferase, were injected (3 × 105) into the forceps minor (FM) or striatum (STR). Immunodeficient rag2−/- and immuno-competent BALB/c mice were used as recipients. Magnetic resonance imaging (MRI) confirmed that cells were precisely deposited at the selected coordinates. The graft viability was assessed noninvasively with biolumi-nescent imaging (BLI) for a period of 16 days. Regardless of implantation site, all grafts ( n = 10) deposited in immunodeficient animals revealed excellent survival. In contrast, immunocompetent animals only accepted grafts at the STR site ( n = 10), whereas all the FM grafts were rejected ( n = 10). To investigate the factors that led to rejection of FM grafts, with acceptance of STR grafts, another group of animals ( n = 19) was sacrificed during the prerejection period, on day 5. Near-infrared fluorescence imaging with IRDye 800CW–polyethylene glycol probe displayed similar blood–brain barrier disruption at both graft locations. The morphological distribution of FM grafts was cylindrical, parallel to the needle track, whereas cells transplanted into the STR accumulated along the border between the STR and the corpus callosum. There was significantly less infiltration by both innate and adaptive immune cells in the STR grafts, especially along the calloso-striatal border. With allograft survival being dependent on the transplantation site, the anatomical coordinates of the graft target should always be taken into account as it may determine the success or failure of therapy.