CNS disease diminishes the therapeutic functionality of bone marrow mesenchymal stem cells.
CNS disease diminishes the therapeutic functionality of bone marrow mesenchymal stem cells.
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中枢神经系统疾病削弱骨髓间充质干细胞的治疗功能
DOI：
10.1016/j.expneurol.2017.06.013
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发表时间：
2017-09
影响因子：
5.3
通讯作者：
Miller RH
中科院分区：
文献类型：
--
作者：
Sargent A;Bai L;Shano G;Karl M;Garrison E;Ranasinghe L;Planchon SM;Cohen J;Miller RH
间充质干细胞（MSC）已成为一种潜在的强大的细胞治疗自身免疫性疾病，包括多发性硬化症（MS）。基于他们在治疗MS动物模型（如实验性自身免疫性脑脊髓炎（EAE））方面的成功，MSC已迅速进入MS的临床试验。这些试验中的大多数使用来自MS患者的自体MSC，尽管尚不清楚CNS疾病如何影响这些细胞。在这里，我们报告说，骨髓间充质干细胞来源于EAE小鼠缺乏治疗效果相比，幼稚间充质干细胞在其改善EAE的能力。用来自EAE-MSC的条件培养基处理也不能调节EAE，并且与幼稚MSC相比，EAE-MSC分泌更高水平的许多促炎细胞因子。类似地，来自MS患者的MSC在治疗EAE方面的疗效低于幼稚MSC，并且分泌更高水平的一些相同的促炎细胞因子。因此，像EAE和MS这样的疾病降低了骨髓MSC的治疗功能，促使重新评估自体MSC作为MS治疗的持续使用。
Mesenchymal stem cells (MSCs) have emerged as a potentially powerful cellular therapy for autoimmune diseases including multiple sclerosis (MS). Based on their success in treating animal models of MS like experimental autoimmune encephalomyelitis (EAE), MSCs have moved rapidly into clinical trials for MS. The majority of these trials use autologous MSCs derived from MS patients, although it remains unclear how CNS disease may affect these cells. Here, we report that bone marrow MSCs derived from EAE mice lack therapeutic efficacy compared to naïve MSCs in their ability to ameliorate EAE. Treatment with conditioned medium from EAE-MSCs also fails to modulate EAE, and EAE-MSCs secrete higher levels of many pro-inflammatory cytokines compared to naïve MSCs. Similarly, MSCs derived from MS patients have less therapeutic efficacy than naïve MSCs in treating EAE and secrete higher levels of some of the same pro-inflammatory cytokines. Thus diseases like EAE and MS diminish the therapeutic functionality of bone marrow MSCs, prompting reevaluation about the ongoing use of autologous MSCs as a treatment for MS.
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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：
4.4
作者：
Cohen, Jeffrey A.
通讯作者：
Cohen, Jeffrey A.
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：
3.3
作者：
Mazzanti, Benedetta;Aldinucci, Alessandra;Ballerini, Clara
通讯作者：
Ballerini, Clara
影响因子：
3.3
作者：
de Oliveira, Gislane L. V.;de Lima, Kalil W. A.;Mamegrim, Kelen C. R.
通讯作者：
Mamegrim, Kelen C. R.