Neuroprotection by human neural progenitor cells after experimental contusion in rats

Neural progenitor/stem cells (HNPC) have been suggested to contribute essential trophic factors and promote survival of degenerating neurons after traumatic brain injury. For these reasons we hypothesize that the addition of HNPC to a post-injury region could possibly protect injured neurons. Experimental brain contusions were carried out in 18 rats. Immediately post-injury, rats were injected with 0.1 ml of medium (n=8), dead cells (n=4), or live cells (n=6) in the medial border of the lesion. The rats were sacrificed 6 days post-surgery and evaluated by immunohistochemistry using a human nuclear marker (huN), hematoxylin and Fluoro-Jade (FJ). Human neural stem cells showed engraftment detectable by positive huN staining in 5/6 animals. The non-grafted animal was excluded from further analyses. Those given dead HNPC or medium showed no detectable huN immunoreactivity. A statistical comparison between the numbers of FJ positive degenerating endogenous neurons was made between rats receiving vehicle and dead cells to evaluate whether the presence of human cells would increase neuronal degeneration in comparison to vehicle alone. The rats receiving vehicle had a median of 117.5 FJ positive cells and dead progenitor cell recipients 175.0 per counted section (P<0.05, Mann-Whitney). Consequently, the animals receiving dead human cells were chosen as controls to the animals receiving live progenitor cells. The rats that received live HNPC demonstrated significantly fewer FJ positive cells per counted section than controls (58.0 vs. 175.0, P<0.01, Mann-Whitney). The post-traumatic perilesional environment allowed for the engraftment of live HNPC. The stepwise analysis indicated that host neuronal degeneration was higher in animals transplanted with non-viable human neuronal progenitor cells than in those receiving vehicle, indicating a bystander effect from introducing foreign antigen. In contrast, transplantation of viable progenitor cells attenuated neuronal degeneration, indicating that a potentially beneficial effect in progenitor cell transplantation is not limited to restoration by transplanted cells, but also improving survival of host cells.