Geloso Maria Concetta, Giannetti Stefano, Cenciarelli Carlo, Budoni Manuela, Casalbore Patrizia, Maira Giulio, Michetti Fabrizio
Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168, Rome, Italy.
Neurochem Res. 2007 Dec;32(12):2054-61. doi: 10.1007/s11064-007-9353-6. Epub 2007 Apr 25.
The present study investigates the survival and fate of neural stem cells/progenitor cells (NSC/NPCs) homografted into the hippocampus of rats treated with trimethyltin (TMT), a potent neurotoxicant considered a useful tool to obtain a well characterized model of neurodegeneration, to evaluate their possible role in the reparative mechanisms that accompany neurodegenerative events. NSC/NPCs expressing eGFP by lentivirus-mediated infection were stereotaxically grafted into the hippocampus of TMT-treated animals and controls. Two weeks after transplantation surviving NSC/NPCs were detectable in 60% of TMT-treated animals and 30% of controls, while 30 days after transplantation only 40% of TMT-treated animals showed surviving grafted cells, which were undetectable in controls. At both times investigated, while grafted NSC/NPCs differentiated into neurons or astrocytes could be observed in addition to undifferentiated NSC/NPCs, we did not find evidence of structural integration of grafted cells into the main site of hippocampal lesion leading to appreciable repair.
本研究调查了神经干细胞/祖细胞(NSC/NPCs)同种移植到用三甲基锡(TMT)处理的大鼠海马体后的存活情况和命运。三甲基锡是一种强效神经毒素,被认为是获得特征明确的神经退行性变模型的有用工具,用于评估它们在伴随神经退行性事件的修复机制中可能发挥的作用。通过慢病毒介导的感染表达增强绿色荧光蛋白(eGFP)的NSC/NPCs被立体定位移植到TMT处理的动物和对照动物的海马体中。移植后两周,在60%的TMT处理动物和30%的对照动物中可检测到存活的NSC/NPCs,而移植后30天,只有40%的TMT处理动物显示有存活的移植细胞,在对照动物中未检测到。在两个研究时间点,除了未分化的NSC/NPCs外,还可观察到移植的NSC/NPCs分化为神经元或星形胶质细胞,但我们没有发现移植细胞在海马体损伤主要部位发生结构整合从而导致明显修复的证据。