Immune problems in central nervous system cell therapy.
Immune problems in central nervous system cell therapy.
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DOI：
10.1007/bf03206631
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发表时间：
2004-10-01
期刊：
影响因子：
--
通讯作者：
Widner, Hakan
中科院分区：
文献类型：
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作者：
Barker, Roger A;Widner, Hakan
将细胞和组织移植到哺乳动物脑和中枢神经系统，重新引起了人们对脑的免疫状态及其对移植组织的反应的兴趣。以前认为大脑是一个绝对的“免疫特权部位”，允许无限期存活而不排斥细胞移植物的观点已被证明是错误的。因此，大脑应该被视为一个可以发生免疫反应的部位，尽管是以一种修饰的形式，在某些情况下，这些免疫反应与其他外周部位的免疫反应一样强烈。临床细胞移植试验现在已经在帕金森氏病、亨廷顿氏病、脱髓鞘疾病、视网膜疾病、中风、癫痫、甚至耳聋中进行，并且通常被设计为细胞替代策略，尽管也已经尝试了植入遗传修饰细胞以补充生长因子。此外，正在考虑细胞疗法的一些CNS疾病具有免疫学基础，例如多发性硬化症，这使情况进一步复杂化。将胚胎神经组织移植到动物和神经退行性疾病患者的CNS中，可以存活，形成和接受突触，并改善行为缺陷。使用流产的人体组织在逻辑上和伦理上是复杂的，这导致寻找替代的细胞来源，包括异种组织、遗传修饰的细胞和干细胞，所有这些都可以并且将诱导一定水平的免疫反应。本文综述了细胞移植到中枢神经系统的免疫学因素。
Transplantation of cells and tissues to the mammalian brain and CNS has revived the interest in the immunological status of brain and its response to grafted tissue. The previously held view that the brain was an absolute "immunologically privileged site" allowing indefinite survival without rejection of grafts of cells has proven to be wrong. Thus, the brain should be regarded as a site where immune responses can occur, albeit in a modified form, and under certain circumstances these are as vigorous as those seen in other peripheral sites. Clinical cell transplant trials have now been performed in Parkinson's disease, Huntington's disease, demyelinating diseases, retinal disorders, stroke, epilepsy, and even deafness, and normally are designed as cell replacement strategies, although implantation of genetically modified cells for supplementation of growth factors has also been tried. In addition, some disorders of the CNS for which cell therapies are being considered have an immunological basis, such as multiple sclerosis, which further complicates the situation. Embryonic neural tissue allografted into the CNS of animals and patients with neurodegenerative conditions survives, makes and receives synapses, and ameliorates behavioral deficits. The use of aborted human tissue is logistically and ethically complicated, which has lead to the search for alternative sources of cells, including xenogeneic tissue, genetically modified cells, and stem cells, all of which can and will induce some level of immune reaction. We review some of the immunological factors involved in transplantation of cells to CNS.