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(PP280) Differentiation of grafted human neural stem cells in irradiated rat brain.
Yu, Yongjia *,1, Gao, Yuanyuan1, Cornforth, Michael1, Morrill, Steven1, Gao, Junling2, Wu, Ping2, 1 Dept. of Radiation Oncology/Biology Division, Galveston, Texas, USA2 Dept. of Neuroscience and Cell Biology, Galveston, Texas, USA
ABSTRACT- Neural stem cells (NSCs) play a pivotal role in neurogenesis, which generates all the brain nerve cells as well as circuitry during embryonic development, and also persists in certain areas of adult brain. Previous studies indicate that damage to neural stem/precursor cells and disruption of microenvironment by ionizing radiation are two important factors in the inhibition of neurogenesis, although the mechanisms are poorly understood. The fate of NSCs in vivo following exposure to radiation is thus of particular interest because functional NSCs in adult brain are potential targets of radiation damage, and because exogenous NSCs may provide potential therapeutic source for replacing lost neurons in radiation-damaged brain. Using a primarily cultured human neural stem cell (hNSC) line K048, we have shown previously that, when pre-treated with a novel in vitro priming procedure before grafting into rat brain, these cells can differentiate into neurons in not only neurogenic but also non-neurogenic regions of brain. To examine whether K048 cells can also differentiate into neurons in radiation-damaged brain, we carried out a study in which male Sprague Dawley rats either received a 10 Gy of X-ray cranial irradiation or were mock treated. One month later, K048 cells that were either primed for 6 days or unprimed were labeled with green fluorescent protein (GFP) and then injected into hippocampus of these rats. One month post transplantation, rats were sacrificed and the brains were processed for immunofluorescent staining analysis. In vitro primed K048 cells generated new neurons in the control as well as irradiated rat brains. In contrast, very few new neurons could be detected from irradiated rat brains grafted with unprimed K048 cells. This data suggests that in vitro primed hNSCs can adapt an intrinsic neuronal fate and therefore be less sensitive to inhibitory effects resulted from disruption of local signaling cues following irradiation.
Key words: human neural stem cells, radiation, differentiation, rat brain
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