Muraro Paolo A, Cassiani Ingoni Riccardo, Martin Roland
Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, MSC1400 Bethesda, MD 20892-1400, USA.
Curr Opin Neurol. 2003 Jun;16(3):299-305. doi: 10.1097/01.wco.0000073930.19076.1b.
This article reviews recent advances in clinical trials of hematopoietic stem cell transplantation as a therapy for multiple sclerosis, and progress in exploring the potential for neural repair of hematopoietic-derived precursors.
Important recent findings are that hematopoietic stem cell transplantation can completely suppress the inflammatory component of multiple sclerosis, hematopoietic stem cells can migrate into the central nervous systems of rodents and humans, and can differentiate into cells expressing neural and glial markers. Hematopoietic stem cells also have neural and myelin repair potential. The heterogeneity of transplant regimens, the selection of patients at different stages of disease in clinical trials, and the limited duration of follow-up all currently preclude the evaluation of the long-term clinical benefits of hematopoietic stem cell transplantation for multiple sclerosis.
Hematopoietic stem cell transplantation is an experimental treatment that shows strong effects on the inflammatory component of multiple sclerosis. On the basis of experience acquired from initial pilot studies, controlled clinical trials are now being designed to verify long-term clinical efficacy. Selecting patients at high risk in the earlier stages of the disease that is dominated by inflammation, and monitoring objectively disease activity by magnetic resonance imaging will be critically important in these studies. Recent advances on the migratory potential and on the differentiation plasticity of hematopoietic stem cells have opened new opportunities for remyelination and axonal repair strategies for multiple sclerosis.
本文回顾了造血干细胞移植治疗多发性硬化症临床试验的最新进展，以及探索造血来源前体细胞神经修复潜力的进展。
近期的重要发现包括，造血干细胞移植可完全抑制多发性硬化症的炎症成分，造血干细胞可迁移至啮齿动物和人类的中枢神经系统，并可分化为表达神经和胶质细胞标志物的细胞。造血干细胞还具有神经和髓鞘修复潜力。目前，移植方案的异质性、临床试验中处于疾病不同阶段患者的选择以及随访时间有限，均妨碍了对造血干细胞移植治疗多发性硬化症长期临床益处的评估。
造血干细胞移植是一种对多发性硬化症炎症成分有显著作用的实验性治疗方法。基于初步试点研究获得的经验，目前正在设计对照临床试验以验证长期临床疗效。在以炎症为主的疾病早期选择高危患者，并通过磁共振成像客观监测疾病活动，在这些研究中将至关重要。造血干细胞迁移潜力和分化可塑性方面的最新进展，为多发性硬化症的髓鞘再生和轴突修复策略带来了新机遇。
