Behavior of human neural progenitor cells transplanted to rat brain

Human neural stem/progenitor cells provide a useful tool for studies of neural development and differentiation, as well as a potential means for neuroreplacement therapeutic needs in the human CNS. Stem cells isolated from developing human central nervous system of 8-12-week fetuses were transplanted to the forebrain and cerebellum of young and adult rats after 14 days of in vitro expansion. Cells were labeled by bisbenzimide prior to transplantation without immunosuppression. Recipient brains were examined 10 and 20 days after transplantation. Labeled stem cells were found in the neocortex, lateral ventricle and caudate nucleus in the forebrain, and in the molecular layer, Purkinje cell layer, and granular layer of the cerebellum. Mitotically dividing stem cells were observed in graft core, confirming their proliferative potential in new microenvironment. Engrafted cells migrate through the parenchyme of striatum, along the ventricular ependymal layer and callosal fibers, some of them reaching the opposite hemisphere. Some cells migrating along the capillaries express glial acid fibrillary protein, demonstrating their differentiation into astrocytes. Grafted cells expressing calbindin were found in the Purkinje cell layer, suggesting their differentiation into the Purkinje cells. At the same time, some grafted cells were undifferentiated and expressed vimentin. Our results demonstrate that cultured human neural stem/progenitor cells migrate and differentiate into both neurons and astrocytes after transplantation to the rat forebrain or cerebellum of young and adult rats.