Raedt Robrecht, Boon Paul
Laboratory for Clinical and Experimental Neurophysiology, Department of Neurology, Ghent University Hospital, Ghent, Belgium.
Acta Neurol Belg. 2005 Sep;105(3):158-70.
Neurodegenerative diseases are characterized by the irreversible loss of neurons involved in networks, important for specific physiological functions. At present, several renewable cell sources stand in line to replace fetal brain cells as potential cell source for transplantation in the damaged brain. Recent developments raise the hope that selective populations of different neuronal phenotypes could be made "on demand". However, for every potential cell source there are still a lot of questions and drawbacks, which need to be resolved before a cell source could become the standard for clinical neuronal transplantation. The recent finding that the brain responds to damage by increased endogenous neurogenesis could prelude new "neurothrophic therapies", based on stimulating this endogenous repair. From preclinical studies it is evident that different disease mechanisms require different cell therapy approaches, depending on the underlying factor of the disease, the identity of neuronal systems that are involved and the complexity of networks that are affected. In this review the potential of different cell sources, including the endogenous progenitor cells, are discussed. Also results of preclinical and clinical transplantation studies in three different disease models are critically evaluated.
神经退行性疾病的特征是参与特定生理功能网络的神经元发生不可逆损失。目前,有几种可再生细胞来源有望取代胎儿脑细胞,成为受损大脑移植的潜在细胞来源。最近的进展带来了希望,即不同神经元表型的选择性群体可以“按需”制造。然而,对于每一种潜在的细胞来源,仍然存在许多问题和缺陷,在一种细胞来源成为临床神经元移植的标准之前,这些问题都需要解决。最近的发现表明,大脑通过增加内源性神经发生来应对损伤,这可能为基于刺激这种内源性修复的新“神经营养疗法”拉开序幕。临床前研究表明,不同的疾病机制需要不同的细胞治疗方法,这取决于疾病的潜在因素、所涉及的神经元系统的特性以及受影响网络的复杂性。在这篇综述中,我们讨论了包括内源性祖细胞在内的不同细胞来源的潜力。同时,我们也对三种不同疾病模型的临床前和临床移植研究结果进行了批判性评估。