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成年大鼠脊髓干/祖细胞移植治疗脊髓损伤

Transplantation of adult rat spinal cord stem/progenitor cells for spinal cord injury.

作者信息

Parr Ann M, Kulbatski Iris, Tator Charles H

机构信息

Division of Neurosurgery, University of Toronto and Toronto Western Hospital, Toronto, Ontario, Canada.

出版信息

J Neurotrauma. 2007 May;24(5):835-45. doi: 10.1089/neu.2006.3771.

Abstract

Stem/progenitor cells derived from the ependymal region of the spinal cord have the ability to self-renew and are multipotential for neurons and glia. These cells may have the ability to regenerate the injured mammalian spinal cord as they do in some lower vertebrates. However, the optimal conditions for transplantation and the fate of transplanted cells are not fully known. In the current study, spinal cord stem/progenitor cells were cultured from adult male rats expressing enhanced green fluorescent protein (eGFP). Neurospheres were transplanted at the time of clip compression injury (35-g force) into the injury site, or 1 mm rostral and caudal to the injury site. Neurospheres were also transplanted into a subacute model (day 9 after injury) and a chronic model (day 28 after injury). Functional recovery was also studied in an acute injury model with weekly locomotor testing over a 16-week period. A significant increase in cell survival at 7 days was seen in rats receiving rostral and caudal injections as compared to injection directly into the site of injury. A significant increase in cell survival was also seen in rats receiving subacute transplants at 9 days after injury. Transplanted cells differentiated primarily into astrocytes (31.2%) and oligodendrocytes (50.3%), and a small number of neurons (1%). No improvement was seen in the Basso, Beattie and Bresnahan (BBB) locomotor rating scale after acute transplantation as compared with injury only, although surviving transplanted cells were identified that had migrated across the injury site from the rostral and caudal injection sites.

摘要

源自脊髓室管膜区域的干细胞/祖细胞具有自我更新能力,并且对神经元和神经胶质细胞具有多能性。这些细胞可能具有再生受损哺乳动物脊髓的能力,就像它们在一些低等脊椎动物中那样。然而,移植的最佳条件以及移植细胞的命运尚不完全清楚。在当前研究中,从表达增强型绿色荧光蛋白(eGFP)的成年雄性大鼠中培养脊髓干细胞/祖细胞。在夹伤(35克力)时将神经球移植到损伤部位,或损伤部位头侧和尾侧1毫米处。神经球也被移植到亚急性模型(损伤后第9天)和慢性模型(损伤后第28天)中。在急性损伤模型中,通过在16周内每周进行运动测试来研究功能恢复情况。与直接注射到损伤部位相比,接受头侧和尾侧注射的大鼠在7天时细胞存活率显著增加。在损伤后第9天接受亚急性移植的大鼠中也观察到细胞存活率显著增加。移植细胞主要分化为星形胶质细胞(31.2%)和少突胶质细胞(50.3%),以及少量神经元(1%)。与仅损伤组相比,急性移植后在Basso、Beattie和Bresnahan(BBB)运动评分量表上未见改善,尽管鉴定出有存活的移植细胞从注射部位头侧和尾侧迁移穿过损伤部位。

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