Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells—fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells—were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.

创伤后脊髓空洞症 (PTS) 是一种脊髓囊肿进行性扩张的严重疾病，影响脊髓损伤患者数年后的情况。为了评估神经细胞疗法防止囊肿扩张并可能替代丢失的神经元，我们开发了 PTS 大鼠模型。我们将挫伤性创伤与蛛网膜下腔注射血液相结合，导致脊髓与周围椎骨束缚，导致囊肿长期扩张。囊肿通常位于损伤部位的喙部、小管外，内衬星形胶质细胞。T2* 加权磁共振成像 (MRI) 显示高信号充满液体的囊肿，但也显示来自碎片和含铁巨噬细胞/小胶质细胞的低信号。将两种类型的人类神经干/祖细胞——胎儿神经前体细胞（hNPC）和源自诱导多能干细胞的神经上皮样干细胞（hNESC）——移植到PTS囊肿中。损伤后10周移植到囊肿中的细胞至少存活10周，迁移到周围的实质中，但在此期间不分化。囊肿部分被细胞消灭，囊肿壁通常与其间的薄层细胞合并。MRI测量的囊肿体积显示，假移植大鼠的囊肿体积继续扩大102%，而hNPCs和hNESCs移植有效阻止了囊肿扩大，囊肿体积分别减少了18.8%和46.8%。减少的体积远远超过了增加的人体细胞的体积。因此，在密切模仿临床情况的动物模型中，我们提供了人类神经干/祖细胞移植可用于治疗 PTS 的原理验证。