Treatment of the bone marrow stromal stem cell supernatants by nasal administration - a new approach to EAE therapy
Treatment of the bone marrow stromal stem cell supernatants by nasal administration - a new approach to EAE therapy
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鼻腔给药治疗骨髓基质干细胞上清液——EAE治疗新方法
DOI：
10.1186/s13287-019-1423-6
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发表时间：
2019
影响因子：
7.5
通讯作者：
Hulun Li
中科院分区：
文献类型：
--
作者：
Xi Wang;Wantong Zhai;Jiahui Zhu;Wei Zhao;Xiaoyi Zou;Siying Qu;Shenyue Wang;Zhongze He;Zhaoying Li;Lingyang Wang;Bo Sun;Hulun Li
简介多发性硬化症（MS）是中枢神经系统（CNS）最常见的自身免疫性疾病之一。中枢神经系统有其独特的结构和功能特点，但缺乏特异性高的精准调控元件作为治疗靶点，使得疾病治疗的发展陷入瓶颈。最近，骨髓基质干细胞（BMSC）的免疫调节和神经保护能力在实验性自身免疫性脑脊髓炎（EAE）中得到了体现。然而，给药途径和安全性评价限制了BMSC的应用。本研究探讨BMSC上清经鼻给药的治疗效果。方法在建立EAE模型的基础上，采用BMSC上清经鼻给药治疗。临床评分和体重用于确定治疗效果。通过LFB染色检测脊髓脱髓鞘情况。采用ELISA法检测外周血血清中炎症因子的表达量。流式细胞仪检测脾脏和引流淋巴结中的促炎细胞。结果经鼻给药BMSC上清液可减轻B细胞介导的EAE临床症状，减轻脱髓鞘程度，减少炎症细胞浸润中枢神经系统；降低外周血中抗体滴度；并显着降低炎症因子的表达。作为一种新型的非侵入性治疗方法，BMSC上清液鼻腔给药与传统的腹腔或静脉注射治疗效果没有差异。结论BMSC上清液经鼻腔给药为EAE治疗提供了新视野和新途径。
IntroductionMultiple sclerosis (MS) is one of the most common autoimmune diseases of the central nervous system (CNS). CNS has its own unique structural and functional features, while the lack of precision regulatory element with high specificity as therapeutic targets makes the development of disease treatment in the bottleneck. Recently, the immunomodulation and neuroprotection capabilities of bone marrow stromal stem cells (BMSCs) were shown in experimental autoimmune encephalomyelitis (EAE). However, the administration route and the safety evaluation limit the application of BMSC. In this study, we investigated the therapeutic effect of BMSC supernatant by nasal administration.MethodsIn the basis of the establishment of the EAE model, the BMSC supernatant were treated by nasal administration. The clinical score and weight were used to determine the therapeutic effect. The demyelination of the spinal cord was detected by LFB staining. ELISA was used to detect the expression of inflammatory factors in serum of peripheral blood. Flow cytometry was performed to detect pro-inflammatory cells in the spleen and draining lymph nodes.ResultsBMSC supernatant by nasal administration can alleviate B cell-mediated clinical symptoms of EAE, decrease the degree of demyelination, and reduce the inflammatory cells infiltrated into the central nervous system; lessen the antibody titer in peripheral bloods; and significantly lower the expression of inflammatory factors. As a new, non-invasive treatment, there are no differences in the therapeutic effects between BMSC supernatant treated by nasal route and the conventional applications, i.e. intraperitoneal or intravenous injection.ConclusionsBMSC supernatant administered via the nasal cavity provide new sights and new ways for the EAE therapy.