Sargent Alex, Bai Lianhua, Shano Genevieve, Karl Molly, Garrison Eric, Ranasinghe Lahiru, Planchon Sarah M, Cohen Jeffrey, Miller Robert H
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Department of Anatomy & Regenerative Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Exp Neurol. 2017 Sep;295:222-232. doi: 10.1016/j.expneurol.2017.06.013. Epub 2017 Jun 9.
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.
间充质干细胞（MSCs）已成为一种对包括多发性硬化症（MS）在内的自身免疫性疾病具有潜在强大作用的细胞疗法。基于其在治疗实验性自身免疫性脑脊髓炎（EAE）等MS动物模型中的成功，MSCs已迅速进入MS的临床试验。这些试验中的大多数使用源自MS患者的自体MSCs，尽管目前尚不清楚中枢神经系统疾病如何影响这些细胞。在此，我们报告，与未处理的MSCs相比，源自EAE小鼠的骨髓MSCs在改善EAE的能力方面缺乏治疗效果。用EAE-MSCs的条件培养基处理也无法调节EAE，并且与未处理的MSCs相比，EAE-MSCs分泌更高水平的多种促炎细胞因子。同样，源自MS患者的MSCs在治疗EAE方面的治疗效果比未处理的MSCs差，并且分泌某些相同促炎细胞因子的水平更高。因此，像EAE和MS这样的疾病会降低骨髓MSCs的治疗功能，促使人们重新评估目前将自体MSCs用作MS治疗方法的做法。
