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The immunoregulatory and neuroprotective effects of human adipose derived stem cells overexpressing IL-11 and IL-13 in the experimental autoimmune encephalomyelitis mice.
International Immunopharmacology ( IF 4.8 ) Pub Date : 2020-07-18 , DOI: 10.1016/j.intimp.2020.106808
Maryam Azimzadeh 1 , Merat Mahmoodi 2 , Mohammad Kazemi 3 , Mazdak Ganjalikhani Hakemi 4 , Morteza Jafarinia 4 , Asma Eslami 4 , Hossein Salehi 1 , Noushin Amirpour 1
Affiliation  

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.



中文翻译:

在实验性自身免疫性脑脊髓炎小鼠中,人脂肪衍生干细胞过表达IL-11和IL-13的免疫调节和神经保护作用。

多发性硬化症(MS)是中枢神经系统(CNS)中的一种炎症性脱髓鞘疾病,其特征在于慢性期的内源性髓鞘再生不完全。促炎和抗炎细胞因子之间平衡的转移是MS发病机理中的重要标志之一。这项研究旨在评估人脂肪衍生干细胞(hADSCs)过表达白介素11和白介素13(IL-11、13-hADSCs)对实验性自身免疫性脑脊髓炎(EAE)(MS的动物模型)的影响。用MOG35-55免疫C57Bl / 6雌性小鼠并出现初始临床症状后12天,通过尾静脉将IL-11、13-hADSCs注射到EAE小鼠中。然后,在免疫后30天(DPI)处死小鼠,提取实验组的脊髓用于组织病理学和实时RT-PCR研究。结果表明,在用IL-11、13-hADSCs治疗的小鼠中,EAE小鼠的临床评分和单核细胞浸润显着降低。同样,在所述治疗组中,髓鞘再生和少突胶质生成显着增强。实时结果表明,与未治疗的EAE组相比,IL-11、13-hADSCs治疗组的促炎/抗炎细胞因子基因表达逆转。

更新日期:2020-07-18
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