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Amnion-Derived Multipotent Progenitor Cells Suppress Experimental Optic Neuritis and Myelitis
Neurotherapeutics ( IF 5.6 ) Pub Date : 2020-10-16 , DOI: 10.1007/s13311-020-00949-9
Reas S Khan 1 , Ahmara G Ross 1 , Keirnan Willett 1 , Kimberly Dine 1 , Rick Banas 2 , Larry R Brown 2 , Kenneth S Shindler 1, 3
Affiliation  

The human amnion has been used for decades in wound healing, particularly burns. Amnion epithelial cells (AECs) have been the focus of extensive research based on their possible pluripotent differentiation ability. A novel, cultured cell population derived from AECs, termed human amnion–derived multipotent progenitor (AMP) cells, secrete numerous cytokines and growth factors that enhance tissue regeneration and reduce inflammation. This AMP cell secretome, termed ST266, is a unique biological solution that accumulates in eyes and optic nerves following intranasal delivery, resulting in selective suppression of optic neuritis in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, but not myelitis at the administered dose. We tested the hypothesis that systemic AMP cell administration could suppress both optic neuritis and myelitis in EAE. Intravenous and intraperitoneal administration of AMP cells significantly reduced ascending paralysis and attenuated visual dysfunction in EAE mice. AMP cell treatment increased retinal ganglion cell (RGC) survival and decreased optic nerve inflammation, with variable improvement in optic nerve demyelination and spinal cord inflammation and demyelination. Results show systemic AMP cell administration inhibits RGC loss and visual dysfunction similar to previously demonstrated effects of intranasally delivered ST266. Importantly, AMP cells also promote neuroprotective effects in EAE spinal cords, marked by reduced paralysis. Protective effects of systemically administered AMP cells suggest they may serve as a potential novel treatment for multiple sclerosis.



中文翻译:


羊膜来源的多能祖细胞抑制实验性视神经炎和脊髓炎



几十年来,人类羊膜一直用于伤口愈合,特别是烧伤。羊膜上皮细胞(AEC)因其可能的多能分化能力而成为广泛研究的焦点。一种源自 AEC 的新型培养细胞群,称为人羊膜源性多能祖细胞 (AMP),可分泌多种细胞因子和生长因子,增强组织再生并减少炎症。这种 AMP 细胞分泌组被称为 ST266,是一种独特的生物溶液,经鼻内递送后会在眼睛和视神经中积聚,从而在多发性硬化症的实验性自身免疫性脑脊髓炎 (EAE) 模型中选择性抑制视神经炎,但在给药时不会抑制脊髓炎剂量。我们测试了全身 AMP 细胞给药可以抑制 EAE 中的视神经炎和脊髓炎的假设。静脉内和腹膜内给予 AMP 细胞可显着减少 EAE 小鼠的上行性麻痹并减轻视觉功能障碍。 AMP 细胞治疗可增加视网膜神经节细胞 (RGC) 的存活率并减少视神经炎症,对视神经脱髓鞘和脊髓炎症和脱髓鞘有不同程度的改善。结果显示,全身 AMP 细胞给药可抑制 RGC 损失和视觉功能障碍,类似于之前鼻内递送 ST266 所证明的效果。重要的是,AMP 细胞还促进 EAE 脊髓的神经保护作用,其特点是减少麻痹。全身施用 AMP 细胞的保护作用表明它们可能成为多发性硬化症的潜在新型治疗方法。

更新日期:2020-10-17
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