Yi Soojin, Kim Jeongho, Kim Mi Ju, Yae Che Gyem, Kim Ki Hean, Kim Hong Kyun
Department of Ophthalmology, School of Medicine, Kyungpook National University, Jung-gu, Daegu, Republic of Korea; Bio-Medical Institute, Kyungpook National University Hospital, Jung-gu, Daegu, Republic of Korea; Department of Biomedical Science, The Graduate School, Kyungpook National University, Jung-gu, Daegu, Republic of Korea.
Department of Ophthalmology, School of Medicine, Kyungpook National University, Jung-gu, Daegu, Republic of Korea; Bio-Medical Institute, Kyungpook National University Hospital, Jung-gu, Daegu, Republic of Korea.
Ocul Surf. 2024 Oct;34:370-380. doi: 10.1016/j.jtos.2024.09.006. Epub 2024 Sep 25.
This study aimed to investigate the therapeutic potential of extracellular vesicles (EVs) derived from human amniotic epithelial cells (hAEC-EVs) for Dry Eye Disease (DED) treatment.
Highly purified EVs were isolated from the culture supernatants of hAECs, which obtained from term placenta and characterized. Proteomic contents were analyzed for assessing its biological function related to the therapeutic potentials for DED. Subsequently, we examined the therapeutic efficacy of hAEC-EVs on human corneal epithelial cells exposed to hyperosmotic stress and in an experimental DED mouse model induced by desiccation stress.
Proteomic analysis of hAEC-EVs revealed proteins linked to cell proliferation and anti-inflammatory responses. We demonstrated efficient uptake of hAEC-EVs by ocular surface cells. Under DED conditions, EV treatment increased corneal epithelial cell proliferation and migration, and concurrently reducing inflammatory cytokines. In the DED mouse model, hAEC-EVs showed significant improvements in corneal staining score, tear secretion, corneal irregularity, and conjunctival goblet cell density. Additionally, hAEC-EVs exhibited a mitigating effect on ocular surface inflammation induced by desiccation.
These findings suggest that hAEC-EVs hold potential as a cell-free therapy for corneal epithelial defects and ocular surface diseases, presenting a promising treatment option for DED.
本研究旨在探讨人羊膜上皮细胞来源的细胞外囊泡（hAEC-EVs）治疗干眼症（DED）的潜力。
从足月胎盘获取的人羊膜上皮细胞培养上清液中分离出高度纯化的细胞外囊泡并进行表征。分析蛋白质组含量以评估其与干眼症治疗潜力相关的生物学功能。随后，我们检测了hAEC-EVs对暴露于高渗应激的人角膜上皮细胞以及在干燥应激诱导的实验性干眼症小鼠模型中的治疗效果。
对hAEC-EVs的蛋白质组分析揭示了与细胞增殖和抗炎反应相关的蛋白质。我们证明了眼表细胞对hAEC-EVs的有效摄取。在干眼症条件下，细胞外囊泡治疗增加了角膜上皮细胞的增殖和迁移，同时减少了炎性细胞因子。在干眼症小鼠模型中，hAEC-EVs在角膜染色评分、泪液分泌、角膜不规则度和结膜杯状细胞密度方面有显著改善。此外，hAEC-EVs对干燥诱导的眼表炎症具有缓解作用。
这些发现表明，hAEC-EVs作为一种无细胞疗法治疗角膜上皮缺损和眼表疾病具有潜力，为干眼症提供了一种有前景的治疗选择。
