North Texas Eye Research Institute, University of North Texas Health Science Center, 3430 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Int J Mol Sci. 2022 Apr 14;23(8):4330. doi: 10.3390/ijms23084330.
Salivary exosomes have demonstrated vast therapeutic and diagnostic potential in numerous diseases. This study pioneers previously unexplored roles of SE in the context of corneal wound healing by utilizing primary corneal stromal cells from healthy (HCFs), type I diabetes mellitus (T1DMs), type II DM (T2DMs), and keratoconus (HKCs) subjects. Purified, healthy human SEs carrying tetraspanins CD9+, CD63+, and CD81+ were utilized. Scratch and cell migration assays were performed after 0, 6, 12, 24, and 48 h following SE stimulation (5 and 25 µg/mL). Significantly slower wound closure was observed at 6 and 12 h in HCFs with 5 μg/mL SE and T1DMs with 5 and 25 μg/mL SE. All wounds were closed by 24-hour, post-wounding. HKCs, T1DMs, and T2DMs with 25µg/mL SE exhibited a significant upregulation of cleaved vimentin compared to controls. Thrombospondin 1 was significantly upregulated in HCFs, HKCs, and T2DMs with 25 µg/mL SE. Lastly, HKCs, T1DMs, and T2DMs exhibited a significant downregulation of fibronectin with 25 μg/mL SE. Whether SEs can be utilized to clinical settings in restoring corneal defects is unknown. This is the first-ever study exploring the role of SEs in corneal wound healing. While the sample size was small, results are highly novel and provide a strong foundation for future studies.
唾液外泌体在许多疾病的治疗和诊断方面具有巨大的潜力。本研究利用来自健康供体（HCFs）、1 型糖尿病（T1DMs）、2 型糖尿病（T2DMs）和圆锥角膜（HKCs）患者的原代角膜基质细胞，首次探索了 SE 在角膜伤口愈合中的先前未知作用。使用携带四跨膜蛋白 CD9+、CD63+和 CD81+的纯化健康人 SE。在 SE 刺激后 0、6、12、24 和 48 h 进行划痕和细胞迁移试验（5 和 25 μg/mL）。在 5 μg/mL SE 的 HCFs 和 5 和 25 μg/mL SE 的 T1DMs 中，观察到 6 和 12 h 时伤口闭合明显减慢。所有伤口在 24 小时后，即创伤后都闭合了。与对照组相比，用 25μg/mL SE 的 HKCs、T1DMs 和 T2DMs 中 cleaved vimentin 的表达显著上调。T2DMs 中 25μg/mL SE 显著上调了血小板反应蛋白 1。最后，用 25μg/mL SE 的 HKCs、T1DMs 和 T2DMs 中 fibronectin 的表达显著下调。SE 是否可用于修复角膜缺损的临床环境尚不清楚。这是首次探索 SE 在角膜伤口愈合中的作用的研究。尽管样本量较小，但结果极具创新性，为未来的研究提供了坚实的基础。
