Willing A E, Lixian J, Milliken M, Poulos S, Zigova T, Song S, Hart C, Sanchez-Ramos J, Sanberg P R
Department of Neurosurgery, Center for Aging and Brain Repair, University of South Florida, Tampa, Florida, USA.
J Neurosci Res. 2003 Aug 1;73(3):296-307. doi: 10.1002/jnr.10659.
Human umbilical cord blood (hUCB) is a rich source of hematopoietic stem cells that have been used to reconstitute immune cells and blood lineages. Cells from another hematopoietic source, bone marrow, have been found to differentiate into neural cells and are effective in the treatment of stroke. In this study, we administered hUCB cells intravenously into the femoral vein or directly into the striatum and assessed which route of cell administration produced the greatest behavioral recovery in rats with permanent middle cerebral artery occlusion (MCAO). All animals were immunosuppressed with cyclosporine (CSA). When spontaneous activity was measured using the Digiscan automated system, it was found to be significantly less when hUCB was transplanted 24 hr after stroke compared with nontransplanted, stroked animals (P < 0.01). Furthermore, behavioral recovery was similar with both striatal and femoral hUCB delivery. This is in contrast to the step test, in which significant improvements were found only after femoral delivery of the hUCB cells. In the passive avoidance test, transplanted animals learned the task faster than nontransplanted animals (P < 0.05). Together, these results suggest that hUCB transplantation may be an effective treatment for brain injuries, such as stroke, or neurodegenerative disorders. In addition, intravenous delivery may be more effective than striatal delivery in producing long-term functional benefits to the stroked animal.
人脐带血(hUCB)是造血干细胞的丰富来源,已被用于重建免疫细胞和血细胞谱系。已发现来自另一种造血来源骨髓的细胞可分化为神经细胞,并对中风治疗有效。在本研究中,我们将hUCB细胞经静脉注入股静脉或直接注入纹状体,并评估哪种细胞给药途径能使永久性大脑中动脉闭塞(MCAO)大鼠获得最大行为恢复。所有动物均用环孢素(CSA)进行免疫抑制。当使用Digiscan自动系统测量自发活动时,发现与未移植的中风动物相比,中风后24小时移植hUCB时自发活动明显减少(P < 0.01)。此外,纹状体和股部hUCB递送的行为恢复相似。这与阶梯试验相反,在阶梯试验中,仅在经股部递送hUCB细胞后才发现有显著改善。在被动回避试验中,移植动物比未移植动物更快学会任务(P < 0.05)。总之,这些结果表明hUCB移植可能是治疗脑损伤(如中风)或神经退行性疾病的有效方法。此外,静脉给药在为中风动物产生长期功能益处方面可能比纹状体给药更有效。