Azimzadeh Maryam, Mahmoodi Merat, Kazemi Mohammad, Hakemi Mazdak Ganjalikhani, Jafarinia Morteza, Eslami Asma, Salehi Hossein, Amirpour Noushin
Department of Anatomical Science, School Of Medicine, Isfahan University of Medical Science, Isfahan, Iran.
Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Int Immunopharmacol. 2020 Oct;87:106808. doi: 10.1016/j.intimp.2020.106808. Epub 2020 Jul 18.
Multiple sclerosis (MS) is an inflammatory demyelination disease in the central nervous system (CNS) characterized by incomplete endogenous remyelination in the chronic phase. A shift of the balance between pro and anti-inflammatory cytokines is one of the important markers in the pathogenesis of MS. This study aimed to evaluate the effects of human adipose derived stem cells (hADSCs) overexpressing interleukin 11 and interleukin 13 (IL-11, 13-hADSCs) on the experimental autoimmune encephalomyelitis (EAE), an animal model of MS.12 days after immunization of C57Bl/6 female mice with MOG35-55 and initial clinical symptoms appearance, the IL-11, 13-hADSCs were injected via the tail vein into the EAE mice. Then, the mice were sacrificed at 30 days post-immunization (DPI) and the spinal cords of experimental groups were extracted for histopathological and real-time RT-PCR studies.The results indicated that the clinical scores and mononuclear cells infiltration into the spinal cords of EAE mice were significantly reduced in mice treated with IL-11, 13-hADSCs. Likewise, the remyelination and oligodendrogenesis were significantly enhanced in the mentioned treatment group. Real-time results demonstrated that pro/anti-inflammatory cytokine genes expression was reversed in IL-11, 13-hADSCs treatment group in comparison to the untreated EAE group.Expression of IL-11 as a neurotrophic cytokine and IL-13 as an anti-inflammatory cytokine by hADSCs could increase the immunomodulatory and neuroprotective effects of hADSCs and be a powerful candidate in stem cell therapy for future treatment of MS.
多发性硬化症(MS)是一种中枢神经系统(CNS)的炎性脱髓鞘疾病,其特征在于慢性期内源性髓鞘再生不完全。促炎细胞因子和抗炎细胞因子之间平衡的改变是MS发病机制中的重要标志物之一。本研究旨在评估过表达白细胞介素11和白细胞介素13的人脂肪来源干细胞(hADSCs,即IL-11、13-hADSCs)对实验性自身免疫性脑脊髓炎(EAE,一种MS动物模型)的影响。在用MOG35-55免疫C57Bl/6雌性小鼠并出现初始临床症状12天后,通过尾静脉将IL-11、13-hADSCs注入EAE小鼠体内。然后,在免疫后30天(DPI)处死小鼠,并提取实验组的脊髓进行组织病理学和实时RT-PCR研究。结果表明,用IL-11、13-hADSCs治疗的小鼠的临床评分以及单核细胞向EAE小鼠脊髓的浸润显著降低。同样,在上述治疗组中,髓鞘再生和少突胶质细胞生成显著增强。实时结果表明,与未治疗的EAE组相比,IL-11、13-hADSCs治疗组中促炎/抗炎细胞因子基因表达发生了逆转。hADSCs表达作为神经营养细胞因子的IL-11和作为抗炎细胞因子的IL-13可增强hADSCs的免疫调节和神经保护作用,并成为未来MS治疗干细胞疗法的有力候选者。