Deacon T, Schumacher J, Dinsmore J, Thomas C, Palmer P, Kott S, Edge A, Penney D, Kassissieh S, Dempsey P, Isacson O
Neuroregeneration Laboratory, Harvard Medical School, McLean Hospital MRC 119, Belmont, Massachusetts 02178, USA.
Nat Med. 1997 Mar;3(3):350-3. doi: 10.1038/nm0397-350.
The movement disorder in Parkinson's disease results from the selective degeneration of a small group of dopaminergic neurons in the substantia nigra pars compacta region of the brain. A number of exploratory studies using human fetal tissue allografts have suggested that transplantation of dopaminergic neurons may become an effective treatment for patients with Parkinson's disease and the difficulty in obtaining human fetal tissue has generated interest in finding corresponding non-human donor cells. Here we report a post-mortem histological analysis of fetal pig neural cells that were placed unilaterally into the caudate-putamen brain region of a patient suffering from Parkinson's disease. Long-term (over seven months) graft survival was found and the presence of pig dopaminergic neurons and other pig neural and glial cells is documented. Pig neurons extended axons from the graft sites into the host brain. Furthermore, other graft derived cells were observed several millimeters from the implantation sites. Markers for human microglia and T-cells showed only low reactivity in direct proximity to the grafts. This is the first documentation of neural xenograft survival in the human brain and of appropriate growth of non-human dopaminergic neurons for a potential therapeutic response in Parkinson's disease.
帕金森病中的运动障碍是由大脑黑质致密部区域一小群多巴胺能神经元的选择性退化所致。一些使用人胎儿组织同种异体移植的探索性研究表明,多巴胺能神经元移植可能成为帕金森病患者的有效治疗方法,而获取人胎儿组织的困难引发了寻找相应非人类供体细胞的兴趣。在此,我们报告了对单侧植入一名帕金森病患者尾状核 - 壳核脑区的胎猪神经细胞进行的死后组织学分析。发现移植组织长期(超过七个月)存活,并记录到猪多巴胺能神经元以及其他猪神经和神经胶质细胞的存在。猪神经元从移植部位向宿主脑内延伸轴突。此外,在距植入部位几毫米处观察到了其他移植来源的细胞。人小胶质细胞和T细胞的标志物在移植组织附近仅显示出低反应性。这是首次记录到人脑中神经异种移植的存活情况以及非人类多巴胺能神经元的适当生长,以实现对帕金森病潜在的治疗反应。