Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat
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DOI:
10.1038/sc.2011.46
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发表时间:
2011-09-01
期刊:
影响因子:
2.2
通讯作者:
Tator, C. H.
Tator, C. H.
中科院分区:
医学3区
文献类型:
--
作者:
Mothe, A. J.;Bozkurt, G.;Tator, C. H.

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研究设计:在模拟人胸段脊髓损伤(SCI)的大鼠模型中通过腰椎穿刺(LP)鞘内移植干细胞的实验研究目的:检测脊髓来源的神经干/祖细胞(NSPCs)和骨髓来源的间充质基质细胞(BMSCs)在脊髓损伤大鼠中LP移植后的分布和表型。方法:在T8脊髓损伤后1周,将骨髓间充质干细胞或骨髓基质干细胞经L3-5节段LP移植。分别于移植后3、17、27 d处死大鼠,定量分析C4、T8、L3-5细胞的相对分布。NSPC和BMSC的表型进行了评估与免疫细胞化学在体外和以下LP transplantation.Results:4周,更多的NSPC迁移到病变部位相对于BMSC和未受伤的动物。然而,没有优先归巢的这些类型的细胞进入损伤部位的实质,和大多数的移植细胞仍然在鞘内空间。在体外,脊髓来源的NSPC增殖和表达巢蛋白,但LP移植后,NSPC成为有丝分裂后,主要表达少突胶质细胞标志物。与此相反,BMSC没有表达任何神经抗原在vivo.Conclusion:LP是一种微创的细胞移植方法,产生广泛的传播的细胞在蛛网膜下腔的脊髓。这是第一个研究报告和量化的表型和空间分布的LP移植的NSPC和BMSC在完整和损伤的脊髓。Spinal Cord(2011)49,967-973; doi:10.1038/sc.2011.46; 2011年5月24日在线发表
Study design: Experimental investigation of intrathecal transplantation of stem cells by lumbar puncture (LP) in a rat model that simulates human thoracic spinal cord injury (SCI).Objectives: To examine the distribution and phenotype of spinal cord-derived neural stem/progenitor cells (NSPCs) and bone marrow-derived mesenchymal stromal cells (BMSCs) following LP transplantation in SCI rats.Setting: Toronto Western Research Institute, Toronto, Ontario, Canada.Methods: NSPCs or BMSCs were transplanted via LP at level L3-5 1 week after compression SCI at T8. Rats were killed at 3, 17 and 27 days after LP transplantation and the relative distribution of cells at C4, T8 and L3-5 was quantitated. The phenotype of the NSPC and BMSC was assessed with immunocytochemistry in vitro and following LP transplantation.Results: By 4 weeks, more NSPC migrated to the lesion site relative to BMSC and uninjured animals. However, there was no preferential homing of either of these types of cells into the parenchyma of the injury site, and most of the transplanted cells remained in the intrathecal space. In vitro, spinal cord-derived NSPC proliferated and expressed nestin, but after LP transplantation, NSPC became post-mitotic and primarily expressed oligodendrocyte markers. In contrast, BMSC did not express any neural antigens in vivo.Conclusion: LP is a minimally invasive method of cell transplantation that produces wide dissemination of cells in the subarachnoid space of the spinal cord. This is the first study to report and quantify the phenotype and spatial distribution of LP transplanted NSPC and BMSC in the intact and injured spinal cord. Spinal Cord (2011) 49, 967-973; doi:10.1038/sc.2011.46; published online 24 May 2011