Department of Neurology, the Second Affiliated Hospital of Zhengzhou University, No. 32 Nanyang Road, Zhengzhou, 450014, China.
Department of Neurology, the 148th Hospital of Chinese PLA, No. 20 North Road Zhoucun District, Zibo, 255300, China.
Sci Rep. 2018 Jan 29;8(1):1756. doi: 10.1038/s41598-018-19703-5.
Multiple Sclerosis (MS), is a chronic inflammatory autoimmune disorder of the central nervous system that leads to chronic demyelination with axonal damage and neuronal loss. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for MS. In the current study, we investigated the effects of MSCs derived from the human umbilical cord (UCMSC) transfected by sphingosine kinase 1 (SPK1) gene. All the results showed that transplantation of UCMSCs gene modified by SPK1 (UCMSC-SPK1) dramatically reduce the severity of neurological deficits of the experimental autoimmune encephalomyelitis (EAE) mice, paralleling by reductions in demyelination, axonal loss, and astrogliosis. UCMSC-SPK1 transplantation also could inhibit the development of natural killer (NK) responses in the spleen of EAE mice, and increase the ratio of CD4 CD25 FoxP3 (Treg) T cells. Furthermore, we described that a shift in the cytokine response from Th1/Th17 to Th2 was an underlying mechanism that suppressed CNS autoimmunity. UCMSCs transfected by SPK1 gene potentially offer a novel mode for the treatment of MS, and the specific mechanism of SPK1 in treating MS/EAE.
多发性硬化症(MS)是一种中枢神经系统的慢性炎症性自身免疫性疾病,导致轴突损伤和神经元丢失的慢性脱髓鞘。间充质干细胞(MSCs)是治疗 MS 的一种很有前途的方法。在本研究中,我们研究了转染鞘氨醇激酶 1(SPK1)基因的人脐带间充质干细胞(UCMSC)的作用。所有结果均表明,SPK1 基因修饰的 UCMSCs(UCMSC-SPK1)移植可显著减轻实验性自身免疫性脑脊髓炎(EAE)小鼠的神经功能缺损严重程度,同时减少脱髓鞘、轴突丢失和星形胶质细胞增生。UCMSC-SPK1 移植还可以抑制 EAE 小鼠脾脏中自然杀伤(NK)反应的发展,并增加 CD4 CD25 FoxP3(Treg)T 细胞的比例。此外,我们还描述了细胞因子反应从 Th1/Th17 向 Th2 的转变是抑制中枢神经系统自身免疫的潜在机制。转染 SPK1 基因的 UCMSCs 可能为 MS 的治疗提供了一种新的模式,以及 SPK1 治疗 MS/EAE 的具体机制。