Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel.
Neurotherapeutics. 2011 Oct;8(4):625-42. doi: 10.1007/s13311-011-0073-x.
The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.
在多发性硬化症（MS）的早期阶段观察到的自发恢复被后来的进行性病程和内源性修复和髓鞘再生过程的失败所取代。尽管这是细胞治疗的基本原理，但尚不清楚 MS 大脑在多大程度上适合修复，以及细胞治疗与其他增强内源性髓鞘再生的策略相比是否具有优势。干细胞治疗的核心是治疗可塑性，通过这种可塑性，神经前体细胞可以替代受损的少突胶质细胞和髓鞘，并且还可以有效地以局部、非系统性的方式减弱自身免疫过程，从而保护脑细胞免受进一步损伤，并促进大脑自身的恢复能力。不同来源的干细胞都具有这种基本的免疫调节和神经营养特性。通过使用不同的递送途径，细胞可以靶向受影响的白质束和发生免疫细胞运输的血管周围龛。目前尚不清楚移植细胞的治疗特性是否会随着时间的推移而保持。一旦神经干细胞治疗（源自胎儿大脑或人类胚胎干细胞）的纯化、大规模生成和安全性得到保证，就可以应用该治疗方法。然而，以前使用骨髓基质（间充质）干细胞的临床经验以及自体细胞的相对容易扩增为其在 MS 中的实验应用开辟了道路。一项初步临床试验已经确定了其静脉内和鞘内给药的可能安全性。短期随访观察到免疫调节作用和临床获益，证明了进一步临床试验的合理性。
