Department of Anesthesiology, College of Medicine, University of Illinois, 835 South Wolcott Avenue, Room E714, Chicago, IL, 60612, USA.
Departments of Ophthalmology and Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA.
Stem Cell Res Ther. 2021 Dec 4;12(1):594. doi: 10.1186/s13287-021-02645-7.
Optic neuritis (ON) is frequently encountered in multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein associated disease, and other systemic autoimmune disorders. The hallmarks are an abnormal optic nerve and inflammatory demyelination; episodes of optic neuritis tend to be recurrent, and particularly for neuromyelitis optica spectrum disorder, may result in permanent vision loss.
Mesenchymal stem cell (MSC) therapy is a promising approach that results in remyelination, neuroprotection of axons, and has demonstrated success in clinical studies in other neuro-degenerative diseases and in animal models of ON. However, cell transplantation has significant disadvantages and complications. Cell-free approaches utilizing extracellular vesicles (EVs) produced by MSCs exhibit anti-inflammatory and neuroprotective effects in multiple animal models of neuro-degenerative diseases and in rodent models of multiple sclerosis (MS). EVs have potential to be an effective cell-free therapy in optic neuritis because of their anti-inflammatory and remyelination stimulating properties, ability to cross the blood brain barrier, and ability to be safely administered without immunosuppression.
We review the potential application of MSC EVs as an emerging treatment strategy for optic neuritis by reviewing studies in multiple sclerosis and related disorders, and in neurodegeneration, and discuss the challenges and potential rewards of clinical translation of EVs including cell targeting, carrying of therapeutic microRNAs, and prolonging delivery for treatment of optic neuritis.
视神经炎（ON）在多发性硬化症、视神经脊髓炎谱系疾病、抗髓鞘少突胶质细胞糖蛋白相关疾病和其他系统性自身免疫性疾病中经常发生。其特征是视神经异常和炎症性脱髓鞘；视神经炎发作往往是复发性的，特别是对于视神经脊髓炎谱系疾病，可能导致永久性视力丧失。
间充质干细胞（MSC）治疗是一种很有前途的方法，可导致髓鞘再生、轴突神经保护，并已在其他神经退行性疾病的临床研究和视神经炎的动物模型中取得成功。然而，细胞移植有很大的缺点和并发症。利用 MSC 产生的细胞外囊泡（EVs）的无细胞方法在多种神经退行性疾病的动物模型和多发性硬化症（MS）的啮齿动物模型中表现出抗炎和神经保护作用。EVs 具有成为视神经炎有效无细胞治疗方法的潜力，因为它们具有抗炎和刺激髓鞘再生的特性，能够穿过血脑屏障，并且能够安全地给予而无需免疫抑制。
我们通过综述多发性硬化症和相关疾病以及神经退行性疾病中有关间充质干细胞 EVs 的研究，综述了 MSC EVs 作为视神经炎新兴治疗策略的潜在应用，并讨论了 EVs 临床转化的挑战和潜在回报，包括细胞靶向、携带治疗性 microRNAs 以及延长递送时间以治疗视神经炎。
