Carelli Stephana, Giallongo Toniella, Marfia Giovanni, Merli Davide, Ottobrini Luisa, Degrassi Anna, Basso Michele D, Di Giulio Anna Maria, Gorio Alfredo
Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy.
Cell Transplant. 2015;24(4):703-19. doi: 10.3727/096368914X685140. Epub 2014 Oct 8.
Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. Neural stem cells from the subventricular zone of the forebrain have been considered a potential tool for cell replacement therapies. We recently isolated a subclass of neural progenitors from the cadaver of mouse donors. These cells, named postmortem neural precursor cells (PM-NPCs), express both erythropoietin (EPO) and its receptor. Their EPO-dependent differentiation abilities produce a significantly higher percentage of neurons than regular NSCs. The cholinergic yield is also higher. The aim of the present study was to evaluate the potential repair properties of PM-NPCs in a mouse model of traumatic SCI. Labeled PM-NPCs were administered intravenously; then the functional recovery and the fate of transplanted cells were studied. Animals transplanted with PM-NPCs showed a remarkable improved recovery of hindlimb function that was evaluated up to 90 days after lesion. This was accompanied by reduced myelin loss, counteraction of the invasion of the lesion site by the inflammatory cells, and an attenuation of secondary degeneration. PM-NPCs migrate mostly at the injury site, where they survive at a significantly higher extent than classical NSCs. These cells accumulate at the edges of the lesion, where a reach neuropile is formed by MAP2- and β-tubulin III-positive transplanted cells that are also mostly labeled by anti-ChAT antibodies.
脊髓损伤(SCI)是一种使人衰弱的临床病症,其特征为一系列神经功能障碍。来自前脑室下区的神经干细胞被认为是细胞替代疗法的一种潜在工具。我们最近从小鼠供体尸体中分离出一类神经祖细胞。这些细胞被命名为死后神经前体细胞(PM-NPCs),它们同时表达促红细胞生成素(EPO)及其受体。它们依赖EPO的分化能力产生的神经元比例明显高于普通神经干细胞。胆碱能产量也更高。本研究的目的是在创伤性脊髓损伤小鼠模型中评估PM-NPCs的潜在修复特性。将标记的PM-NPCs静脉注射;然后研究移植细胞的功能恢复和命运。移植了PM-NPCs的动物在损伤后长达90天的时间里,后肢功能恢复显著改善。这伴随着髓磷脂损失减少、炎症细胞对损伤部位侵袭的对抗以及继发性变性的减轻。PM-NPCs大多迁移到损伤部位,在那里它们的存活程度明显高于经典神经干细胞。这些细胞聚集在损伤边缘,在那里由MAP2和β-微管蛋白III阳性的移植细胞形成丰富的神经纤维网,这些细胞也大多被抗胆碱乙酰转移酶(ChAT)抗体标记。