Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
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DOI：
10.1371/journal.pone.0113936
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Saiz A
中科院分区：
文献类型：
--
作者：
Llufriu S;Sepúlveda M;Blanco Y;Marín P;Moreno B;Berenguer J;Gabilondo I;Martínez-Heras E;Sola-Valls N;Arnaiz JA;Andreu EJ;Fernández B;Bullich S;Sánchez-Dalmau B;Graus F;Villoslada P;Saiz A
间充质干细胞（MSC）在多发性硬化症中的非对照研究表明了一些有益的效果。在这项随机、双盲、安慰剂对照、交叉的II期研究中，我们研究了它们在复发缓解型多发性硬化症患者中的安全性和有效性。根据6个月和研究结束时磁共振成像（MRI）上钆增强病变（GEL）的累积数量评价疗效。对常规治疗无反应的患者，定义为在过去1 - 2个月内MRI扫描至少1次复发和/或凝胶，疾病持续时间2至10年，扩展残疾状态量表（EDSS）3.0-6.5，随机接受IV 1-2×106骨髓源性MSC/Kg或安慰剂。6个月后，治疗逆转，患者再随访6个月。次要终点是临床结局（EDSS和MS功能复合评分的复发和残疾），以及几项脑MRI和光学相干断层扫描测量。采用免疫学试验评价其免疫调节作用。基线时，9名患者随机接受MSC（n = 5）或安慰剂（n = 4）。 安慰剂组1例患者在前5个月内复发3次后退出。我们没有发现任何严重的不良事件。在6个月时，接受MSC治疗的患者有降低平均累积GEL数量的趋势（3.1，95% CI = 1.1-8.8 vs 12.3，95% CI = 4.4-34.5，p = 0.064），并且在研究结束时平均GEL降低（−2.8±5.9 vs 3±5.4，p = 0.075）。 在次要终点中未检测到显着的治疗差异。我们观察到MSC治疗的患者血液中Th 1（CD 4 + IFN-γ+）细胞的频率无显著降低。骨髓间充质干细胞是安全的，可以减少炎症MRI参数，支持其免疫调节特性。ClinicalTrials.gov www.example.com
Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study. Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0–6.5 were randomized to receive IV 1–2×106 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects. At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1–8.8 vs 12.3, 95% CI = 4.4–34.5, p = 0.064), and at the end of study to reduced mean GEL (−2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients. Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266
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影响因子：
48
作者：
Connick, Peter;Kolappan, Madhan;Crawley, Charles;Webber, Daniel J.;Patani, Rickie;Michell, Andrew W.;Du, Ming-Qing;Luan, Shi-Lu;Altmann, Daniel R.;Thompson, Alan J.;Compston, Alastair;Scott, Michael A.;Miller, David H.;Chandran, Siddharthan
通讯作者：
Chandran, Siddharthan
影响因子：
--
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
通讯作者：
Slavin, Shimon
影响因子：
11.2
作者：
Gabilondo, Inigo;Martinez-Lapiscina, Elena H.;Villoslada, Pablo
通讯作者：
Villoslada, Pablo
影响因子：
3.7
作者：
de Mendizabal, Nieves Velez;Hutmacher, Matthew M.;Bies, Robert R.
通讯作者：
Bies, Robert R.
影响因子：
6.7
作者：
Rice, C. M.;Mallam, E. A.;Scolding, N. J.
通讯作者：
Scolding, N. J.