Wang Xiaofei, Xu Xiao-Ming
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Exp Neurol. 2014 Nov;261:308-19. doi: 10.1016/j.expneurol.2014.05.022. Epub 2014 May 27.
Schwann cells (SCs) have been considered to be one of the most promising cell types for transplantation to treat spinal cord injury (SCI) due to their unique growth-promoting properties. Despite the extensive use as donor cells for transplantation in SCI models, the fate of SCs is controversial due in part to the lack of a reliable marker for tracing the grafted SCs. To precisely assess the fate and temporal profile of transplanted SCs, we isolated purified SCs from sciatic nerves of adult transgenic rats overexpressing GFP (SCs-GFP). SCs-GFP were directly injected into the epicenter of a moderate contusive SCI at the mid-thoracic level at 1week post-injury. The number of SCs-GFP or SCs-GFP labeled with Bromodeoxyuridine (BrdU) was quantified at 5min, 1day, and 1, 2, 4, 12 and 24weeks after cell injection. Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, footfall error, thermal withdrawal latency, and footprint analysis were performed before and after the SCs-GFP transplantation. After transplantation, SCs-GFP quickly filled the lesion cavity. A remarkable survival of grafted SCs-GFP up to 24weeks post-grafting was observed with clearly identified SC individuals. SCs-GFP proliferated after injection, peaked at 2weeks (26% of total SCs-GFP), decreased thereafter, and ceased at 12weeks post-grafting. Although grafted SCs-GFP were mainly confined within the border of surrounding host tissue, they migrated along the central canal for up to 5.0mm at 4weeks post-grafting. Within the lesion site, grafted SCs-GFP myelinated regenerated axons and expressed protein zero (P0) and myelin basic protein (MBP). Within the SCs-GFP grafts, new blood vessels were formed. Except for a significant decrease of angle of rotation in the footprint analysis, we did not observe significant behavioral improvements in BBB locomotor rating scale, thermal withdrawal latency, or footfall errors, compared to the control animals that received no SCs-GFP. We conclude that SCs-GFP can survive remarkably well, proliferate, migrate along the central canal, and myelinate regenerated axons when being grafted into a clinically-relevant contusive SCI in adult rats. Combinatorial strategies, however, are essential to achieve a more meaningful functional regeneration of which SCs may play a significant role.
雪旺细胞（SCs）因其独特的促生长特性，被认为是用于移植治疗脊髓损伤（SCI）最有前景的细胞类型之一。尽管在SCI模型中广泛用作移植供体细胞，但雪旺细胞的命运仍存在争议，部分原因是缺乏可靠的标记物来追踪移植的雪旺细胞。为了精确评估移植雪旺细胞的命运和时间变化情况，我们从过表达绿色荧光蛋白（GFP）的成年转基因大鼠坐骨神经中分离出纯化的雪旺细胞（SCs-GFP）。在损伤后1周，将SCs-GFP直接注射到胸段中部中度挫伤性SCI的损伤中心。在细胞注射后5分钟、1天以及1、2、4、12和24周，对SCs-GFP或用溴脱氧尿苷（BrdU）标记的SCs-GFP数量进行定量分析。在SCs-GFP移植前后，进行Basso、Beattie和Bresnahan（BBB）运动评分量表、步幅误差、热缩足潜伏期和足迹分析。移植后，SCs-GFP迅速填充损伤腔。观察到移植的SCs-GFP在移植后长达24周有显著存活，且雪旺细胞个体清晰可辨。注射后SCs-GFP增殖，在2周时达到峰值（占总SCs-GFP的26%），此后下降，并在移植后12周停止。尽管移植的SCs-GFP主要局限于周围宿主组织的边界内，但在移植后4周时，它们沿着中央管迁移了长达5.0毫米。在损伤部位，移植的SCs-GFP使再生轴突髓鞘化，并表达蛋白零（P0）和髓鞘碱性蛋白（MBP）。在SCs-GFP移植物内，形成了新的血管。与未接受SCs-GFP的对照动物相比，除了足迹分析中旋转角度显著减小外，我们未观察到BBB运动评分量表、热缩足潜伏期或步幅误差有显著的行为改善。我们得出结论，当移植到成年大鼠临床相关的挫伤性SCI中时，SCs-GFP能够很好地存活、增殖、沿着中央管迁移并使再生轴突髓鞘化。然而，组合策略对于实现更有意义的功能再生至关重要，其中雪旺细胞可能发挥重要作用。
