Koutouzis T K, Emerich D F, Borlongan C V, Freeman T B, Cahill D W, Sanberg P R
Department of Surgery, University of South Florida College of Medicine, Tampa 33612.
Crit Rev Neurobiol. 1994;8(3):125-62.
Initially, the specific aim of transplantation studies was to investigate the regenerative capabilities of the mammalian nervous system. From this underlying impetus, a myriad of knowledge, spanning from molecular biology to neurobiology, has enhanced our understanding of regeneration and the applicability of fetal tissue transplantation in treating various neurodegenerative diseases. Current evidence suggests that transplantation of fetal neural tissue ameliorates the neurobiological and behavioral changes observed in animal models of central nervous system (CNS) disorders. In light of numerous basic science studies, clinical trials have begun to evaluate the potential of neural transplantation in treating human diseases. Indeed, modest progress has been reported in the treatment of Parkinson's disease. However, whereas fetal tissue transplantation has reached considerable success, it has also been observed to produce either no beneficial effects, magnify existing behavioral abnormalities, or even produce a unique constellation of deficits. Thus, while the prospects are promising, further investigations aimed at improving and refining existing transplantation paradigms are warranted before neural transplantation techniques can be of widespread value. This review article attempts to provide an overview of the neuroanatomical, neurochemical, and behavioral effects produced by transplanted fetal tissue in several animal models of CNS disorders. We have attempted to present both positive and adverse effects and to critically analyze the suitability of neural transplantation as a therapy for the various neurological disorders. In addition, alternative approaches, including the use of encapsulated neural tissue implants and genetically engineered cell lines along with their clinical potential, are discussed when appropriate.
最初,移植研究的具体目标是探究哺乳动物神经系统的再生能力。基于这一潜在动力,从分子生物学到神经生物学的大量知识,加深了我们对再生以及胎儿组织移植在治疗各种神经退行性疾病中的适用性的理解。目前的证据表明,胎儿神经组织移植可改善中枢神经系统(CNS)疾病动物模型中观察到的神经生物学和行为变化。鉴于众多基础科学研究,临床试验已开始评估神经移植治疗人类疾病的潜力。事实上,在帕金森病的治疗方面已报道取得了一定进展。然而,尽管胎儿组织移植已取得相当大的成功,但也观察到它要么没有产生有益效果,放大现有的行为异常,甚至产生一系列独特的缺陷。因此,虽然前景乐观,但在神经移植技术具有广泛价值之前,有必要进行进一步研究以改进和完善现有的移植模式。这篇综述文章试图概述在几种CNS疾病动物模型中移植胎儿组织所产生的神经解剖学、神经化学和行为学效应。我们试图呈现积极和消极的影响,并批判性地分析神经移植作为各种神经系统疾病治疗方法的适用性。此外,还会在适当的时候讨论替代方法,包括使用封装的神经组织植入物和基因工程细胞系及其临床潜力。