Spinal Cord Research Center, Department of Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, PA, 19129, United States.
Spinal Cord Research Center, Department of Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, PA, 19129, United States.
J Neurosci Methods. 2018 Jan 1;293:144-150. doi: 10.1016/j.jneumeth.2017.09.014. Epub 2017 Sep 22.
Cellular transplantation to repair a complete spinal cord injury (SCI) is tremendously challenging due to the adverse local milieu for graft survival and growth. Results from cell transplantation studies yield great variability, which may possibly be due to the surgical techniques employed to induce an SCI. In order to delineate the influence of surgery on such inconsistency, we compared lesion morphology and graft survival as well as integration from different lesion methodologies of SCI.
Surgical techniques, including a traditional approach cut+microaspiration, and two new approaches, cut alone as well as crush, were employed to produce a complete SCI, respectively. Approximately half of the rats in each group received injury only, whereas the other half received grafts of fetal brainstem cells into the lesion gap.
Eight weeks after injury with or without graft, histological analysis showed that the cut+microaspiration surgery resulted in larger lesion cavities and severe fibrotic scars surrounding the cavity, and cellular transplants rarely formed a tissue bridge to penetrate the barrier. In contrast, the majority of cases treated with cut alone or crush exhibited smaller cavities and less scarring; the grafts expanded and blended extensively with the host tissue, which often built continuous tissue bridging the rostral and caudal cords.
Scarring and cavitation were significantly reduced when microaspiration was avoided in SCI surgery, facilitating graft/host tissue fusion for signal transmission.
The result suggests that microaspiration frequently causes severe scars and cavities, thus impeding graft survival and integration.
由于移植细胞在损伤部位的存活和生长环境不佳,因此通过细胞移植来修复完全性脊髓损伤(SCI)极具挑战性。细胞移植研究的结果存在很大的差异,这可能是由于用于诱导 SCI 的手术技术不同。为了阐明手术对这种不一致性的影响,我们比较了不同 SCI 模型方法的损伤形态、移植物存活和整合情况。
分别采用传统的切割+微抽吸方法、单独切割以及挤压等三种新方法来制作完全性 SCI。每组大鼠的一半接受单纯损伤,另一半则将胎脑干细胞移植到损伤间隙。
损伤后 8 周,无论是否进行移植,组织学分析显示,切割+微抽吸手术导致更大的损伤腔和围绕腔的严重纤维性瘢痕,且细胞移植物很少形成组织桥来穿透屏障。相比之下,大多数接受单独切割或挤压治疗的病例表现出较小的腔和较少的瘢痕;移植物扩张并与宿主组织广泛融合,常常建立连续的组织桥,连接脊髓的头端和尾端。
避免 SCI 手术中的微抽吸可显著减少瘢痕和空洞的形成,有利于移植物/宿主组织融合以进行信号传递。
该结果表明,微抽吸常导致严重的瘢痕和空洞,从而阻碍移植物的存活和整合。