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Transplantation of adult neural stem/progenitor cells and bone marrow derived mesenchymal stromal cells in the injured adult rat spinal cord.

机译:成年神经干/祖细胞和骨髓源性间充质基质细胞在成年大鼠脊髓中的移植。

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摘要

Neural stem/progenitor cells (NSPCs) have previously been identified in both the mammalian brain and spinal cord. They have the ability to self-renew and are multipotential for both neurons and glia. It has been suggested that they can be used to repair the spinal cord by generating cells useful for repair and an environment that would promote axonal regeneration. It has also been suggested that transplantation of bone marrow-derived mesenchymal stromal cells (BMSCs) into the injured spinal cord may provide therapeutic benefit.;We were unable to demonstrate functional improvement after transplantation of either NSPCs or BMSCs after 35g clip compression injury. We also transplanted both cell types alone and in combination into a 27g clip injury model. We hypothesized that BMSCs would form a scaffold upon which NSPCs could be seeded, to improve survival of the NSPCs, and improve functional recovery. This study demonstrated that this strategy of sequential transplantation of BMSCs and NSPCs trends toward improved cell survival of the NSPCs, but does not lead to improved functional recovery.;However, we did find a significant improvement in functional recovery in rats receiving spinal cord derived NSPCs (SC-NSPCs) only in this 27g clip injury model. NSPCs differentiated mainly into oligodendrocytes and astrocytes, and were seen enveloping non-myelinated axons. The early recovery seen in these experiments, along with the increase in host oligodendrocytes at 7 days, is supportive of a neuroprotective action of SC-NSPCs. A retrograde tracer analysis indicates that SC-NSPC transplantation contributed to either axonal preservation or regeneration, and that the BMSCs did not.;We show here that transplantation of adult rat neural stem/progenitor cells (NSPCs) into the injured spinal cord results in mainly glial differentiation of the transplanted cells but poor long term survival. NSPCs have better survival if transplanted rostral and caudal to the lesion, when transplanted in a delayed fashion at 9 days, and if high dose (20 mg/kg/day) cyclosporine is used. In contrast, bone marrow derived mesenchymal stromal cells (BMSCs) survive well and form a bridge across the lesion cavity, but do not differentiate into cells of neural lineage.
机译:先前已经在哺乳动物脑和脊髓中鉴定出神经干/祖细胞(NSPC)。它们具有自我更新的能力,并且对神经元和神经胶质都有潜能。已经提出它们可以通过产生可用于修复的细胞和促进轴突再生的环境而用于修复脊髓。也有人认为,将骨髓间充质基质细胞(BMSCs)移植到受损的脊髓中可能提供治疗益处。我们无法证明35g夹子压迫性损伤后NSPCs或BMSCs移植后的功能改善。我们还将两种细胞类型单独或组合移植到27g夹伤模型中。我们假设BMSCs将形成一个支架,可以在其上植入NSPC,以提高NSPC的存活率并改善功能恢复。这项研究表明BMSCs和NSPCs的顺序移植策略趋向于改善NSPCs的细胞存活率,但不会导致功能恢复的改善;但是,我们确实发现接受脊髓源性NSPCs的大鼠的功能恢复有显着改善(SC-NSPC)仅在此27g夹伤模型中。 NSPCs主要分化为少突胶质细胞和星形胶质细胞,并且被包裹在无髓鞘的轴突中。在这些实验中看到的早期恢复以及7天时宿主少突胶质细胞的增加支持了SC-NSPC的神经保护作用。逆向示踪剂分析表明,SC-NSPC移植有助于轴突的保存或再生,而BMSC则没有。;我们在这里表明,成年大鼠神经干/祖细胞(NSPC)移植到受伤的脊髓中主要导致移植细胞的神经胶质细胞分化,但长期存活率较差。如果将延髓的尾部和尾部移植到病灶上,以第9天的延迟方式移植,以及使用大剂量(20 mg / kg /天)的环孢菌素,则NSPC的存活率更高。相比之下,骨髓来源的间充质基质细胞(BMSC)可以很好地存活并在病灶腔中形成桥梁,但不会分化为神经谱系细胞。

著录项

  • 作者

    Parr, Ann Margaret.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 133 p.
  • 总页数 133
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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