Cellular replacement therapy for neurologic disorders: potential of genetically engineered cells.
Cellular replacement therapy for neurologic disorders: potential of genetically engineered cells.
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神经系统疾病的细胞替代疗法：基因工程细胞的潜力。
DOI：
10.1002/jcb.240450305
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发表时间：
1991
影响因子：
4
通讯作者：
Gage,FH
中科院分区：
文献类型：
--
作者：
Chen,LS;Ray,J;Fisher,LJ;Kawaja,MD;Schinstine,M;Kang,UJ;Gage,FH
神经移植是一种细胞替代方式，已被用于帕金森氏症的治疗试验。研究表明，移植物中可被宿主大脑利用的代谢物的紧张性释放可能是治疗效果的主要机制。胎儿组织的使用因伦理争议和免疫学不相容而变得复杂。自体成人组织移植一直没有成功，主要是因为存活率较低。基因工程细胞是很有前途的供体细胞的替代来源。我们研究了原代皮肤成纤维细胞作为脑内移植供体细胞的潜力。原代皮肤成纤维细胞在大脑中存活并保持在原位。许多基因(神经生长因子、酪氨酸羟基酶、谷氨酸脱羧酶和胆碱乙酰转移酶)已被成功地导入并在原代成纤维细胞中表达。在帕金森病大鼠模型中，L分泌多巴胺的原代成纤维细胞在移植到失神经支配的纹状体后8周内表现出行为效应。能够最大化基因转移、转基因表达和脑内成纤维细胞存活的因素构成了未来的研究方向。
Neural transplantation, a mode of cellular replacement, has been used as a therapeutic trial for Parkinson's disease. Studies indicate that tonic release of the metabolites from the graft that can be utilized by the host brain, is likely to be the major mechanism responsible for the therapeutic effect. The use of fetal tissue is complicated by ethical controversy and immunological incompatibility. Autografting adult tissue has not been successful mainly due to poor survival. Genetically engineered cells are promising alternative sources of donor cells. We have investigated the potential of primary skin fibroblasts as donor cells for intracerebral grafting. Primary skin fibroblasts survive in the brain and remain in situ. A number of genes (nerve growth factor, tyrosine hydroxylase, glutamic acid decarboxylase, and choline acetyltransferase) have been successfully introduced and expressed in the primary fibroblasts. The L‐dopasecreting primary fibroblasts exhibited a behavioral effect in a rat model of Parkinson's disease up to 8 weeks after being grafted into denervated striatum. Factors that can maximize gene transfer, transgene expression, and fibroblast survival in the brain make up the future direction of investigation.