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[髓鞘形成细胞移植作为多发性硬化症的再生疗法——实验基础及临床研究现状]

[Transplantation of myelinating cells as regenerative therapy for multiple sclerosis - experimental basis and present state of clinical studies].

作者信息

Stangel M

机构信息

Klinik für Neurologie, Universitätsklinikum Benjamin Franklin, FU Berlin, Germany.

出版信息

Nervenarzt. 2002 Oct;73(10):937-45. doi: 10.1007/s00115-002-1370-8.

Abstract

Currently available therapies for multiple sclerosis (MS) delay disease progression via immunomodulation or immunosuppression. A persisting neurological deficit is mostly irreversible. Thus, a reparative treatment is urgently warranted. After positive results in animal models, clinical trials to promote endogenous remyelination with intravenous immunoglobulins (IVIg) or the growth factor IGF-1 were performed, unfortunately without clinical improvement. Another possibility to achieve remyelination is the transplantation of myelinating cells into the central nervous system. Proof of principle and demonstration of the functionality were shown in numerous experiments, and a first clinical trial in patients with MS has started. Although there are still several open questions, many are specific to MS and can not be answered in an animal model. This first trial will show if cell transplantation is a feasible concept in MS and whether the transplanted cells will survive and form new myelin. Schwann cells are currently the most promising cells to be transplanted, due to the advantages of an autologous transplantation from the patient's sural nerve biopsy, possibility to expand the cells in culture, and the possibility that they may escape the ongoing inflammatory reaction in MS. Other cell types are available, including stem cells, which are in the centre of a lively discussion. The results of the ongoing trial must be awaited before other transplant studies are performed to tackle other yet unresolved problems. At the time, it seems unlikely that cell transplantation will become clinical practice in the near future.

摘要

目前用于治疗多发性硬化症(MS)的疗法通过免疫调节或免疫抑制来延缓疾病进展。持续存在的神经功能缺损大多是不可逆的。因此,迫切需要一种修复性治疗方法。在动物模型中取得阳性结果后,开展了使用静脉注射免疫球蛋白(IVIg)或生长因子IGF-1促进内源性髓鞘再生的临床试验,但遗憾的是并未取得临床改善。实现髓鞘再生的另一种可能性是将髓鞘形成细胞移植到中枢神经系统。众多实验已证明了其原理及功能,针对MS患者的首个临床试验已经启动。尽管仍有几个悬而未决的问题,但其中许多问题是MS所特有的,无法在动物模型中得到解答。首个试验将表明细胞移植在MS中是否是一个可行的概念,以及移植的细胞是否会存活并形成新的髓鞘。由于可以从患者的腓肠神经活检中进行自体移植、能够在培养中扩增细胞以及它们可能逃避MS中持续的炎症反应等优点,雪旺细胞目前是最有希望用于移植的细胞。还有其他细胞类型可供选择,包括干细胞,这也是一个热烈讨论的焦点。在进行其他移植研究以解决其他尚未解决的问题之前,必须等待正在进行的试验结果。目前看来,细胞移植在不久的将来不太可能成为临床实践。

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