A re-assessment of long distance growth and connectivity of neural stem cells after severe spinal cord injury.
A re-assessment of long distance growth and connectivity of neural stem cells after severe spinal cord injury.
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DOI：
10.1016/j.expneurol.2014.04.008
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发表时间：
2014-07
影响因子：
5.3
通讯作者：
Steward, Oswald
中科院分区：
文献类型：
--
作者：
Sharp, Kelli G.;Yee, Kelly Matsudaira;Steward, Oswald
关键词：
作为支持独立复制的NIH“卓越研究设施-脊髓损伤”项目的一部分，我们重复了一项研究的关键部分，该研究报告了在大鼠完全脊髓横断后用生长因子处理的神经干细胞（NSCs）的强劲植入。大鼠（n = 20）在胸椎3节段（T3）完全切除，2周后采用两种不同的移植方法（切除和不切除疤痕组织），在纤维蛋白基质中加入生长因子混合物，接受NSC移植。对照大鼠（n = 9）仅接受横切。用BBB量表评估后肢运动功能。损伤后9周，6只大鼠在网状结构中注射BDA，追踪网状脊髓束轴突。在大多数大鼠中，移植物能够填满病变腔，尽管移除疤痕组织的移植物具有较大的中心腔。移植物与宿主组织广泛混合，消除了切割末端的星形胶质细胞边界，但在大多数情况下，移植物内存在明确的分区，将移植物的吻端和尾端分开。在某些情况下，分区含有非神经元疤痕组织。GFP标记的轴突从移植物中大量生长，但通过通道示踪和5HT免疫细胞化学显示，宿主轴突向移植物的生长很少。移植组与对照组在运动恢复程度上无统计学差异。我们的研究结果证实了之前的报道，即NSC移植可以填补病变腔并坚固地延伸轴突，但揭示了大多数移植物不能在吻侧和尾侧节段之间建立连续的神经组织桥。
As part of the NIH “Facilities of Research Excellence—Spinal Cord Injury” project to support independent replication, we repeated key parts of a study reporting robust engraftment of neural stem cells (NSCs) treated with growth factors after complete spinal cord transection in rats. Rats (n = 20) received complete transections at thoracic level 3 (T3) and 2 weeks later received NSC transplants in a fibrin matrix with a growth factor cocktail using 2 different transplantation methods (with and without removal of scar tissue). Control rats (n = 9) received transections only. Hindlimb locomotor function was assessed with the BBB scale. Nine weeks post injury, reticulospinal tract axons were traced in 6 rats by injecting BDA into the reticular formation. Transplants grew to fill the lesion cavity in most rats although grafts made with scar tissue removal had large central cavities. Grafts blended extensively with host tissue obliterating the astroglial boundary at the cut ends, but in most cases there was a well-defined partition within the graft that separated rostral and caudal parts of the graft. In some cases, the partition contained non-neuronal scar tissue. There was extensive outgrowth of GFP labeled axons from the graft, but there was minimal ingrowth of host axons into the graft revealed by tract tracing and immunocy-tochemistry for 5HT. There were no statistically significant differences between transplant and control groups in the degree of locomotor recovery. Our results confirm the previous report that NSC transplants can fill lesion cavities and robustly extend axons, but reveal that most grafts do not create a continuous bridge of neural tissue between rostral and caudal segments.
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