Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats
Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats
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DOI：
10.1016/j.expneurol.2004.05.045
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发表时间：
2004-11-01
影响因子：
5.3
通讯作者：
Jakeman, LB
中科院分区：
文献类型：
--
作者：
Ankeny, DP;McTigue, DM;Jakeman, LB
结论脊髓损伤(SCI)产生大量充满液体、碎片和炎性细胞的囊腔，缺乏支持显著轴突再生的结构。最近发现的能够生成中枢神经系统(CNS)组织的干细胞，加上神经移植策略的成功，重新燃起了人们对中枢神经系统创伤修复和恢复的希望。基于多项使用骨髓基质细胞(MSCs)促进中枢神经系统修复的研究结果，我们将MSCs移植到大鼠脊髓损伤腔内，进一步观察其对功能恢复、损伤形态和轴突生长的影响。我们发现，移植的MSCs诱导了后肢空步--一种与步进控制电路激活相关的自发运动--但不改变地面运动恢复的时间进程或程度。用体视学技术描述脊髓解剖，我们发现MSC移植占据了病变腔，并与宿主组织和白质(髓鞘)的保存有关，证明了这些细胞具有神经保护作用。与未移植的标本相比，移植的MSC形成的组织基质支持更多的轴突生长。此外，轴突轮廓的均匀随机取样显示，移植的MSC中的大多数轴突的长轴与脊髓的长轴平行，表明轴突的生长是纵向的。总之，这些研究支持进一步研究骨髓基质细胞作为潜在的脊髓损伤修复策略。(C)2004 Elsevier Inc.保留所有权利。
Contusive spinal cord injury (SCI) produces large fluid-, debris- and inflammatory cell-filled cystic cavities that lack structure to support significant axonal regeneration. The recent discovery of stem cells capable of generating central nervous system (CNS) tissues, coupled with success in neurotransplantation strategies, has renewed hope that repair and recovery from CNS trauma is possible. Based on results from several studies using bone marrow stromal cells (MSCs) to promote CNS repair, we transplanted MSCs into the rat SCI lesion cavity to further investigate their effects on functional recovery, lesion morphology, and axonal growth. We found that transplanted MSCs induced hindlimb airstepping-a spontaneous locomotor movement associated with activation of the stepping control circuitry-but did not alter the time course or extent of overground locomotor recovery. Using stereological techniques to describe spinal cord anatomy, we show that MSC transplants occupied the lesion cavity and were associated with preservation of host tissue and white matter (myelin), demonstrating that these cells exert neuroprotective effects. The tissue matrix formed by MSC grafts supported greater axonal growth than that found in specimens without grafts. Moreover, uniform random sampling of axon profiles revealed that the majority of neurites in MSC grafts were oriented with their long axis parallel to that of the spinal cord, suggesting longitudinally directed growth. Together, these studies support further investigation of marrow stromal cells as a potential SCI repair strategy. (C) 2004 Elsevier Inc. All rights reserved.