Lankford Karen L, Imaizumi Toshio, Honmou Osamu, Kocsis Jeffery D
Department of Neurology, Yale University School of Medicine, PVA/EPVA Neuroscience Regeneration Research Center, VA Medical Center, West Haven, Connecticut, 06516, USA.
J Comp Neurol. 2002 Feb 11;443(3):259-74. doi: 10.1002/cne.10117.
Quantitative morphometric techniques were used to assess the extent and pattern of remyelination produced by transplanting allogenic Schwann cells into demyelinated lesions in adult rat spinal cords. The effects of donor age, prior culturing of donor cells, prior lesioning of donor nerves, and host immunosuppression were evaluated by transplanting suspensions of 30,000 acutely dissociated or cultured Schwann cells from neonatal, young adult, or aged adult rat sciatic nerves into X-irradiation and ethidium bromide-induced demyelinated dorsal column lesions, with or without co-transplantation of neonatal optic nerve astrocytes. Three weeks after transplantation, spinal cords were processed for histological analysis. Under all Schwann cell transplant protocols, large areas containing many Schwann cell-like myelinated axon profiles could be readily observed throughout most of the lesion length. Within these "myelin-rich" regions, the vast majority of detectable axons showed a peripheral-like pattern of myelination. However, interaxonal spacing also increased, resulting in densities of myelinated axons that were more similar to peripheral nerve than intact dorsal columns. Freshly isolated Schwann cells remyelinated more axonal length than cultured Schwann cells, and cells from younger donors remyelinated slightly more axon length than cells from older donors, but all Schwann cell transplant protocols remyelinated tens of thousands of millimeters of axon length and remyelinated axons at similar densities. These results indicate that Schwann cells prepared under a variety of conditions are capable of eliciting remyelination, but that the density of remyelinated axons is much lower than the myelinated axon density in intact spinal cords.
采用定量形态计量学技术评估将同种异体雪旺细胞移植到成年大鼠脊髓脱髓鞘损伤部位后产生的髓鞘再生程度和模式。通过将来自新生、年轻成年或老年成年大鼠坐骨神经的30000个急性解离或培养的雪旺细胞悬液移植到X射线和溴化乙锭诱导的脱髓鞘背柱损伤部位,评估供体年龄、供体细胞的预先培养、供体神经的预先损伤以及宿主免疫抑制的影响,同时进行或不进行新生视神经星形胶质细胞的共移植。移植三周后,对脊髓进行组织学分析。在所有雪旺细胞移植方案下,在大部分损伤长度内都能很容易地观察到含有许多雪旺细胞样有髓轴突轮廓的大片区域。在这些“富含髓鞘”的区域内,绝大多数可检测到的轴突呈现出类似外周的髓鞘形成模式。然而,轴突间间距也增加了,导致有髓轴突密度与外周神经更相似,而与完整的背柱不同。新鲜分离的雪旺细胞比培养的雪旺细胞能使更多的轴突长度重新髓鞘化,年轻供体的细胞比老年供体的细胞能使稍多一些的轴突长度重新髓鞘化,但所有雪旺细胞移植方案都能使数万千毫米的轴突长度重新髓鞘化,且重新髓鞘化的轴突密度相似。这些结果表明,在各种条件下制备的雪旺细胞都能够引发髓鞘再生,但重新髓鞘化的轴突密度远低于完整脊髓中有髓轴突的密度。