Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis.
Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis.
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DOI：
10.1001/archneurol.2010.248
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发表时间：
2010-10
影响因子：
--
通讯作者：
Slavin, Shimon
中科院分区：
文献类型：
--
作者：
Karussis, Dimitrios;Karageorgiou, Clementine;Vaknin-Dembinsky, Adi;Gowda-Kurkalli, Basan;Gomori, John M.;Kassis, Ibrahim;Bulte, Jeff W. M.;Petrou, Panayiota;Ben-Hur, Tamir;Abramsky, Oded;Slavin, Shimon
评价多发性硬化（MS）和肌萎缩侧索硬化（ALS）患者鞘内和静脉注射自体间充质干细胞（MSC）（也称为间充质基质细胞）的可行性、安全性和免疫学效应。1/2期开放安全性临床试验。入选了15例MS患者（平均[SD]扩展残疾状态量表[EDSS]评分，6.7 [1.0]）和19例ALS患者（平均[SD]肌萎缩侧索硬化功能评定量表[ALSFRS]评分，20.8 [8.0]）。培养后，鞘内（n=34）和静脉内（n=14）注射平均（SD）63.2 × 106（2.5 × 106）个MSC。在9例病例中，用超顺磁性氧化铁（Feridex）磁性标记MSC。主要的结局指标是记录副作用。随访（≤25个月）包括不良事件评估，通过EDSS进行神经功能障碍评估，磁共振成像以排除意外病理并跟踪标记的干细胞，以及免疫学测试以评估MSC移植的短期免疫调节作用。21名患者出现了与注射相关的不良反应，包括一过性发热，15名患者报告头痛。随访期间未报告重大不良反应。在观察的前6个月期间，平均ALSFRS评分保持稳定，而平均（SD）EDSS评分从6.7（1.0）改善至5.9（1.6）。磁共振成像显示脑室枕角中的MSC，表明ferumoxides标记的细胞可能在脑膜，蛛网膜下腔和脊髓中迁移。免疫组化结果显示，MSC移植后24 h，骨髓树突状细胞上CD 4 + CD 25+调节性T细胞比例增加，淋巴细胞增殖反应降低，CD 40+、CD 83+、CD 86+和HLA-DR表达减少。在MS和ALS患者中移植MSC是一种临床可行且相对安全的方法，并诱导立即的免疫调节作用。
To evaluate the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells (MSCs) (also called mesenchymal stromal cells) in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). A phase 1/2 open-safety clinical trial. Fifteen patients with MS (mean [SD] Expanded Disability Status Scale [EDSS] score, 6.7 [1.0]) and 19 with ALS (mean [SD] Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS] score, 20.8 [8.0]) were enrolled. After culture, a mean (SD) of 63.2 × 106 (2.5 × 106) MSCs was injected intrathecally (n=34) and intravenously (n=14). In 9 cases, MSCs were magnetically labeled with the superparamagnetic iron oxide ferumoxides (Feridex). The main outcome measure was the recording of side effects. Follow-up (≤25 months) included adverse events evaluation, neurological disability assessment by means of the EDSS, magnetic resonance imaging to exclude unexpected pathologies and track the labeled stem cells, and immunological tests to assess the short-term immunomodulatory effects of MSC transplantation. Twenty-one patients had injection-related adverse effects consisting of transient fever, and 15 reported headache. No major adverse effects were reported during follow-up. The mean ALSFRS score remained stable during the first 6 months of observation, whereas the mean (SD) EDSS score improved from 6.7 (1.0) to 5.9 (1.6). Magnetic resonance imaging visualized the MSCs in the occipital horns of the ventricles, indicating the possible migration of ferumoxides-labeled cells in the meninges, subarachnoid space, and spinal cord. Immunological analysis revealed an increase in the proportion of CD4+ CD25+ regulatory T cells, a decrease in the proliferative responses of lymphocytes, and the expression of CD40+, CD83+, CD86+, and HLA-DR on myeloid dendritic cells at 24 hours after MSC transplantation. Transplantation of MSCs in patients with MS and ALS is a clinically feasible and relatively safe procedure and induces immediate immunomodulatory effects.
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影响因子：
4.8
作者：
Koç, ON;Day, J;Krivit, W
通讯作者：
Krivit, W
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作者：
Izadpanah, Reza;Trygg, Cynthia;Bunnell, Bruce A.
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