Neural progenitor cells proliferate and differentiate when transplanted into ischemic brain or retina.
The adult mammalian brain contains neural stem and progenitor cells (NPCs) that can proliferate, self-renew, and generate all of the cellular elements of the mature brain, including neurons. The ability of NPCs to respond in vivo to injury-induced signals that can direct their differentiation towards multiple distinct neural lineages suggest that these undifferentiated progenitors offer a dynamic and versatile source of cells for neural regeneration following CNS injury. The purpose of this study was to determine if NPCs obtained from rat embryonic cortex would proliferate and differentiate into mature neurons and glia when transplanted in vivo into rat brain or retina subjected to ischemia. Primary undifferentiated progenitor cell clones from embryonic day 14.5 rat cortex were labeled with the cell membrane marker, PKH-26. Donor cells were transplanted into the cerebral cortex (CC), subventricular zone (SVZ) and vitreous cavity (VC) of the eye. In the ischemic animals as well as the control animals, some of the donor cells proliferated and differentiated into oligodendrocytes (CNPase) and astrocytes (GFAP) as early as 7 days following transplantation. By contrast, by 21 increasing to 45 days, most donor cells in CC and SVZ exhibited a neuronal phenotype (NeuN, MAP-2). However, transplantation into the SVZ was highly effective in generating new neurons in ischemic brain whereas direct transplantation into post-ischemic cortex was significantly less effective. Interestingly, donor cells transplanted in VC acquired a neuronal phenotype compatible with those seen in CC. Our data suggest the exogenous NPCs can differentiate into neurons and glia and that local environmental factors differentially regulate the profile of progenitor cell regenerative responses to CNS injury.