Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats.
Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats.
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DOI：
10.1186/s13287-015-0255-2
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发表时间：
2015-12-22
影响因子：
7.5
通讯作者：
Jendelova P
中科院分区：
文献类型：
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作者：
Amemori T;Ruzicka J;Romanyuk N;Jhanwar-Uniyal M;Sykova E;Jendelova P
干细胞治疗为脊髓损伤（SCI）患者提供了一种有前景的治疗方法。然而，所应用的干细胞以不同的方式发挥其作用，这取决于施用途径。在本研究中，我们将源自诱导多能干细胞（iPS-NP）的神经前体细胞通过椎管内注射到病变中心或鞘内注射到患有球囊诱导脊髓压迫病变的大鼠的蛛网膜下腔中。使用行为测试（BBB、平梁测试、旋转、足底测试）、形态分析、免疫组织化学和 qPCR 评估功能性运动表现、细胞存活、星形胶质细胞增生、轴突出芽和内源性神经营养生长因子的表达。两种治疗均促进 SCI 大鼠的功能性运动恢复。椎管内注射的 iPS-NP 可以很好地存活 2 个月，并且 MAP2 呈阳性，而鞘内移植的细胞在给药部位或脊髓组织中检测不到。椎管内植入增加了灰质和白质的保留和轴突萌芽，并减少了星形胶质细胞增生，而鞘内植入仅导致白质保留的改善和轴突萌芽的增加，同时对内源性神经营养生长因子基因的表达或神经胶质疤痕的减少没有积极作用。鞘内移植的 iPS-NP 通过旁分泌机制对 SCI 具有中等的治疗效果，该机制不需要细胞存在于组织中；然而，i.s.的延长生存期。脊髓中的移植细胞可以促进长期脊髓组织再生。本文的在线版本 (doi:10.1186/s13287-015-0255-2) 包含补充材料，可供授权用户使用。
Stem cell treatment provides a promising therapy for patients with spinal cord injury (SCI). However, the applied stem cells exert their effects in different manners that are dependent on the route used for administration. In the present study, we administered neural precursors derived from induced pluripotent stem cells (iPS-NPs) either intraspinally into the lesion center or intrathecally into the subarachnoid space of rats with a balloon-induced spinal cord compression lesion. Functional locomotor performance, cell survival, astrogliosis, axonal sprouting and the expression of endogenous neurotrophic growth factors were evaluated using behavioral tests (BBB, flat beam test, rotarod, plantar test), morphometric analysis, immunohistochemistry and qPCR. Both treatments facilitated the functional locomotor recovery of rats with SCI. iPS-NPs injected intraspinally survived well for 2 months and were positive for MAP2, while cells grafted intrathecally were undetectable at the site of administration or in the spinal cord tissue. Intraspinal implantation increased gray and white matter sparing and axonal sprouting and reduced astrogliosis, while intrathecal application resulted only in an improvement of white matter sparing and an increase in axonal sprouting, in parallel with no positive effect on the expression of endogenous neurotrophic growth factor genes or glial scar reduction. Intrathecally grafted iPS-NPs had a moderate therapeutic benefit on SCI through a paracrine mechanism that does not require the cells to be present in the tissue; however, the extended survival of i.s. grafted cells in the spinal cord may promote long-term spinal cord tissue regeneration. The online version of this article (doi:10.1186/s13287-015-0255-2) contains supplementary material, which is available to authorized users.