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在实验性自身免疫性脑脊髓炎中,源自在自组装肽纳米支架中培养的少突胶质细胞的条件培养基的治疗潜力。

Therapeutic potential of conditioned medium derived from oligodendrocytes cultured in a self-assembling peptide nanoscaffold in experimental autoimmune encephalomyelitis.

机构信息

Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Brain Res. 2019 May 15;1711:226-235. doi: 10.1016/j.brainres.2019.01.035. Epub 2019 Jan 28.

Abstract

The use of neurotrophic factors is considered to be a novel therapeutic approach for restoring and/or maintaining neurological function in neurodegenerative disorders, such as multiple sclerosis (MS). Various studies have shown that conditioned medium produced by oligodendrocyte (OL-CM) contain a variety of neurotrophic factors. Here, we investigated the restorative effects of OL-CM, collected from oligodendrocytes cultured in a self-assembling peptide hydrogels scaffold (PuraMatrix), in experimental autoimmune encephalomyelitis (EAE) mouse model. Neural stem/progenitor cells, isolated from the embryonic mouse brain, were cultured and differentiated into oligodendrocyte. Cell viability and proliferation of oligodendrocytes were assessed by live/dead and MTT assays. Motor functions, myelination, cell infiltration, gliosis, and inflammatory process were assessed in EAE mice after intracranial injection of OL-CM at different concentrations. Application of OL-CM improved clinical score and neurological function in EAE mice and reduced the inflammatory cell infiltration and demyelination. Furthermore, administration of OL-CM reduced the expression of pro-inflammatory cytokines and suppressed the activation of NLRP3-inflammasome complex in EAE mice. These data suggest the potential therapeutic effect of OL-CM for MS treatment.

摘要

神经营养因子的应用被认为是一种恢复和/或维持神经退行性疾病(如多发性硬化症)中神经功能的新治疗方法。多项研究表明,少突胶质细胞(OL-CM)条件培养基中含有多种神经营养因子。在这里,我们研究了从在自组装肽水凝胶支架(PuraMatrix)中培养的少突胶质细胞中收集的 OL-CM 在实验性自身免疫性脑脊髓炎(EAE)小鼠模型中的修复作用。从胚胎小鼠脑中分离的神经干细胞/祖细胞进行培养并分化为少突胶质细胞。通过活/死和 MTT 测定评估少突胶质细胞的活力和增殖。在 EAE 小鼠颅内注射不同浓度的 OL-CM 后,评估运动功能、髓鞘形成、细胞浸润、神经胶质增生和炎症过程。OL-CM 的应用改善了 EAE 小鼠的临床评分和神经功能,并减少了炎症细胞浸润和脱髓鞘。此外,OL-CM 的给药降低了促炎细胞因子的表达,并抑制了 EAE 小鼠中 NLRP3-炎症小体复合物的激活。这些数据表明 OL-CM 对多发性硬化症治疗具有潜在的治疗作用。

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