TRANSPLANTATION OF FETAL SPINAL-CORD TISSUE INTO THE CHRONICALLY INJURED ADULT-RAT SPINAL-CORD
TRANSPLANTATION OF FETAL SPINAL-CORD TISSUE INTO THE CHRONICALLY INJURED ADULT-RAT SPINAL-CORD
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DOI：
10.1002/cne.902690406
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发表时间：
1988-03-22
影响因子：
2.5
通讯作者：
REIER, PJ
中科院分区：
文献类型：
--
作者：
HOULE, JD;REIER, PJ
将胚胎中枢神经系统（CNS）组织移植到急性损伤的大鼠脊髓中，已被证明可以分化并部分与邻近的宿主神经元整合。在本研究中，我们探讨了将移植方法应用于慢性脊髓病变的潜力。特别是，我们感兴趣的是了解宿主-移植物融合是否会受到以神经胶质瘢痕形成为特征的晚期组织病理学的不利影响。在移植从14天大鼠胎儿获得的脊髓组织之前2-7周，在成年大鼠脊髓的腰部水平制备半切腔。移植物的存活，分化，并与宿主脊髓的整合，随后在移植后1-6个月的时间间隔通过光学显微镜技术进行评估。免疫细胞化学也被用来检查在宿主-移植物界面的星形胶质细胞瘢痕形成的程度和移植物的肾上腺素能神经支配。在其他一些情况下，顺行和逆行运输的麦胚凝集素结合辣根过氧化物酶被用来确定是否轴突投射之间形成的主机脊髓和移植物。损伤后2周，初始病变腔被连续的星形胶质细胞瘢痕包围，在未移植的对照动物中，损伤后至少7周保持完整。在其他动物中，移植到这些晚期病变导致分化良好的移植物，长期存活率为90%。虽然致密的神经胶质增生仍然存在沿着受体脊髓的病变表面，但在瘢痕中断的地方观察到融合的宿主移植神经瘤灶。供体组织最常在与宿主灰质的界面处与宿主脊髓整合;然而，一些植入物也表现出与受损宿主白色物质融合的部位。因此，尽管在移植时慢性病变部位的壁上沿着存在致密的胶质瘢痕，但仍可以常规地识别融合的移植物和宿主神经元的某些区域。顺行和逆行追踪结果表明，一些轴突投射到这些移植物起源于宿主神经元位于紧邻供体-受体界面。此外，免疫细胞化学显示，一些主机的cardioninergic轴突（推测的脊髓上的起源）穿越nongliotic接口。这项研究的结果提出了一种可能性，即移植的胎儿CNS组织有能力刺激已建立的胶质瘢痕的部分消退。另一方面，如果在移植过程中疤痕的完整性被无意中破坏，那么胎儿脊髓组织的存在可能会缓和继发性神经胶质反应。在任何一种情况下，目前的一些移植物-宿主神经元整合和轴突相互作用的演示建立了一个有用的框架，为未来的研究，在慢性损伤的脊髓功能恢复的最终目标。
Transplants of fetal central nervous system (CNS) tissue into the acutely injured rat spinal cord have been demonstrated to differentiate and partially integrate with the adjacent host neuropil. In the present study, we examined the potential for applying a transplantation approach to chronic spinal cord lesions. In particular, we were interested in learning whether host-graft fusion would be adversely affected by an advanced histopathology characterized in part by glial scar formation. Hemisection cavities were prepared at lumbar levels of the adult rat spinal cord 2-7 weeks prior to the transplantation of spinal cord tissue obtained from 14-day rat fetuses. Graft survival, differentiation, and integration with the host spinal cord were subsequently evaluated by light microscopic techniques at post-transplantation intervals of 1-6 months. Immunocytochemistry was also employed to examine the extent of astrocytic scar formation at the host-graft interface and serotoninergic innervation of the grafts. In some other cases, anterograde and retrograde transport of wheat germ agglutinin-conjugated horseradish peroxidase was used to determine whether axonal projections were formed between the host spinal cords and grafts. By 2 weeks after injury the initial lesion cavities were surrounded by a continuous astrocytic scar which remained intact for at least 7 weeks after injury in nongrafted control animals. In other animals, transplantation into these advanced lesions resulted in well-differentiated grafts with a 90% long-term survival rate. Although dense gliosis was still present along the lesion surfaces of the recipient spinal cord, foci of confluent host-graft neuropil were observed where interruptions in the scar had occurred. Donor tissue integrated most often with the host spinal cord at interfaces with host gray matter; however, some implants also exhibited sites of fusion with damaged host white matter. Thus, some regions of confluent graft and host neuropil could be routinely identified, despite the presence of a dense glial scar along the walls of the chronic lesion site at the time of transplantation. Anterograde and retrograde tract-tracing results suggested that some axonal projections into these grafts had originated from host neurons located immediately adjacent to the donor-recipient interface. In addition, immunocytochemistry revealed some host serotoninergic axons (presumable of supraspinal origin) traversing nongliotic interfaces. The results of this study raise the possibility that grafted fetal CNS tissue has a capacity for stimulating partial regression of an established glial scar. On the other hand, if the integrity of the scar was inadvertently disturbed during transplantation, then the presence of fetal spinal cord tissue may have tempered a secondary glial response. In either case, the present demonstration of some graft-host neuropil integration and axonal interaction establishes a useful framework for future studies directed at the ultimate goal of functional restoration in the chronically injured spinal cord.