Slavin Shimon, Kurkalli Basan G S, Karussis Dimitrios
International Center for Cell Therapy & Cancer (ICTC), Tel Aviv Medical Center, Tel Aviv, Israel.
Clin Neurol Neurosurg. 2008 Nov;110(9):943-6. doi: 10.1016/j.clineuro.2008.01.014. Epub 2008 Mar 6.
No specific treatment exists for patients with multiple sclerosis (MS) who fail to respond to conventional immunosuppressive and immunomodulating modalities. Furthermore, no method is available for regeneration of existing defect in the central nervous system (CNS). The ultimate goals of MS treatment, similarly to other autoimmune diseases, are twofold: first, to eliminate self-reactive lymphocytes and to prevent de novo development of self-reactivity by induction of self-tolerance. Second, attempting regeneration and repair of existing damage. In the case of MS, there is a need to stop the ongoing process of inflammation against the CNS by self-reactive lymphocytes thus facilitating spontaneous re-myelinization while in parallel attempt to recover existing neurological deficits caused by the autoimmune process resulting in demyelinization. Cell therapy stands out as the most rationale approach for neurological regeneration. In the absence of clinically applicable approaches involving the use of embryonic stem cells, we are investigating the feasibility and efficacy of enriched autologous mesenchymal stromal cells (MSC) injected intrathecally and intravenously to induce in situ immunomodulation and neuroprotection and possibly facilitate repair of the CNS in patients with MS and other neurodegenerative disorders. Our preclinical results suggest that bone marrow cells may provide a source of stem cells with a potential for migration into inflamed CNS and differentiate into cells expressing neuronal and glial cell markers. Based on the preclinical data, we are currently evaluating the safety of a similar therapeutic approach in a small group of patients with MS and other neurodegenerative diseases.
对于对传统免疫抑制和免疫调节方法无反应的多发性硬化症（MS）患者，尚无特异性治疗方法。此外，目前也没有方法可用于修复中枢神经系统（CNS）已有的损伤。与其他自身免疫性疾病一样，MS治疗的最终目标有两个：第一，消除自身反应性淋巴细胞，并通过诱导自身耐受性来防止自身反应性的重新产生。第二，尝试对已有的损伤进行再生和修复。就MS而言，需要通过自身反应性淋巴细胞停止正在进行的针对CNS的炎症过程，从而促进自发的再髓鞘化，同时并行尝试恢复由自身免疫过程导致脱髓鞘所引起的现有神经功能缺损。细胞疗法是神经再生最合理的方法。由于缺乏涉及使用胚胎干细胞的临床适用方法，我们正在研究鞘内和静脉注射富集的自体间充质基质细胞（MSC）以诱导原位免疫调节和神经保护，并可能促进MS和其他神经退行性疾病患者的CNS修复的可行性和有效性。我们的临床前结果表明，骨髓细胞可能提供一种干细胞来源，其具有迁移到炎症性CNS并分化为表达神经元和神经胶质细胞标志物的细胞的潜力。基于临床前数据，我们目前正在一小群MS和其他神经退行性疾病患者中评估类似治疗方法的安全性。
