1 Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology , Queen Square, London, United Kingdom .
2 Department of Neurosurgery, Wroclaw Medical University , Wroclaw, Poland .
J Neurotrauma. 2018 Jun 15;35(12):1367-1378. doi: 10.1089/neu.2017.5273. Epub 2018 Mar 29.
Transplanted human olfactory ensheathing cells (hOECs) were mixed with collagen into a unilateral transection of four dorsal roots (C6-T1) in a rat model. By mixing with collagen, the limited numbers of hOEC were maximized from an olfactory bulb biopsy and optimize cavity filling. Cyclosporine was administered daily to prevent immune rejection. Forelimb proprioception was assessed weekly in a vertical climb task. Half of the rats receiving hOEC transplants showed some functional improvement ("responders") over six weeks of the study while the other half did not ("nonresponders") and performed similarly to "injured only" rats. Transplanted cells were seen at both one week and six weeks after the surgical procedure; many were concentrated within the lesion cavity, but others were found with elongated processes in the overlying connective tissue. There were some fibers in the injury area associated with transplanted cells that were immunostained for neurofilament and TUJ1. Responder and nonresponder rats were compared with regard to microglial activation within the deep dorsal horn of cervical levels C7, C8 and also axon loss within the cuneate fasciculus at cervical level C3. Little difference was seen in microglial activation or axonal loss that could account for the improved proprioception in the responders group. This preliminary study is the first to transplant human olfactory bulb cells into a rat model of dorsal root injury; by refining each component part of the procedure, the repair potential of OECs can be maximized in a clinical setting.
将人嗅鞘细胞(hOEC)与胶原混合,移植到大鼠单侧背根(C6-T1)横断模型中。通过与胶原混合,从嗅球活检中最大限度地增加了有限数量的 hOEC,并优化了腔隙填充。每天给予环孢素以预防免疫排斥。在前肢 proprioception 垂直攀爬任务中每周评估一次。在研究的六周内,一半接受 hOEC 移植的大鼠表现出一些功能改善(“反应者”),而另一半则没有(“非反应者”),并且与“仅受伤”的大鼠表现相似。在手术程序后一周和六周都可以看到移植细胞;许多细胞集中在病变腔内,但其他细胞在覆盖的结缔组织中发现有伸长的突起。在与移植细胞相关的损伤区域中有一些纤维被神经丝和 TUJ1 免疫染色。对反应者和非反应者大鼠进行比较,比较颈段 C7、C8 深部背角的小胶质细胞激活,以及颈段 C3 的楔束内轴突丢失。在小胶质细胞激活或轴突丢失方面几乎没有差异,这可能解释了反应者组 proprioception 的改善。这项初步研究是首次将人嗅球细胞移植到大鼠背根损伤模型中;通过细化程序的每个组成部分,可以最大限度地提高 OEC 在临床环境中的修复潜力。