Dry eye syndrome (DES) is a chronic ocular disease that induces epithelial damage to the cornea by decreasing tear production and quality. Adequate treatment options have not been established for severe DES such as Sjogren’s syndrome due to complicated pathological conditions. To solve this problem, we focused on the conditioned medium of human adipose-derived mesenchymal stem cells (hAdMSC-CM), which have multiple therapeutic properties. Here, we showed that hAdMSC-CM suppressed Benzalkonium Chloride (BAC)-induced cytotoxicity and inflammation in human corneal epithelial cells (hCECs). In addition, hAdMSC-CM increased the expression level and regulated the localisation of barrier function-related components, and improved the BAC-induced barrier dysfunction in hCECs. RNA-seq analysis and pharmacological inhibition experiments revealed that the effects of hAdMSC-CM were associated with the TGFβ and JAK-STAT signalling pathways. Moreover, in DES model rats with exorbital and intraorbital lacrimal gland excision, ocular instillation of hAdMSC-CM suppressed corneal epithelial damage by improving barrier dysfunction of the cornea. Thus, we demonstrated that hAdMSC-CM has multiple therapeutic properties associated with TGFβ and JAK-STAT signalling pathways, and ocular instillation of hAdMSC-CM may serve as an innovative therapeutic agent for DES by improving corneal barrier function.

干眼综合症（DES）是一种慢性眼部疾病，通过减少泪液产生和质量而导致角膜上皮损伤。由于病理条件复杂，对于干燥综合征等严重DES，尚未建立足够的治疗方案。为了解决这个问题，我们重点研究了具有多种治疗特性的人脂肪间充质干细胞（hAdMSC-CM）的条件培养基。在这里，我们发现 hAdMSC-CM 抑制苯扎氯铵 (BAC) 诱导的人角膜上皮细胞 (hCEC) 的细胞毒性和炎症。此外，hAdMSC-CM可增加hCECs中屏障功能相关成分的表达水平并调节其定位，改善BAC诱导的屏障功能障碍。RNA-seq分析和药理抑制实验表明hAdMSC-CM的作用与TGFβ和JAK-STAT信号通路有关。此外，在眶外和眶内泪腺切除的 DES 模型大鼠中，眼部滴注 hAdMSC-CM 通过改善角膜屏障功能障碍来抑制角膜上皮损伤。因此，我们证明hAdMSC-CM具有与TGFβ和JAK-STAT信号通路相关的多种治疗特性，并且hAdMSC-CM的眼部滴注可以通过改善角膜屏障功能作为DES的创新治疗剂。