Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, California, USA.
Department of Ophthalmology & Visual Science, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Stem Cells Transl Med. 2019 May;8(5):478-489. doi: 10.1002/sctm.18-0178. Epub 2019 Jan 15.
Severe corneal injuries often result in permanent vision loss and remain a clinical challenge. Human bone marrow-derived mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their antiscarring, anti-inflammatory, and antiangiogeneic properties. We aimed to deliver lyophilized MSC secretome (MSC-S) within a viscoelastic gel composed of hyaluronic acid (HA) and chondroitin sulfate (CS) as a way to enhance corneal re-epithelialization and reduce complications after mechanical and chemical injuries of the cornea. We hypothesized that delivering MSC-S within HA/CS would have improved wound healing effects compared the with either MSC-S or HA/CS alone. The results showed that a once-daily application of MSC-S in HA/CS enhances epithelial cell proliferation and wound healing after injury to the cornea. It also reduced scar formation, neovascularization, and hemorrhage after alkaline corneal burns. We found that combining MSC-S and HA/CS increased the expression of CD44 receptors colocalized with HA, suggesting that the observed therapeutic effects between the MSC-S and HA/CS are in part mediated by CD44 receptor upregulation and activation by HA. The results from this study demonstrate a reproducible and efficient approach for delivering the MSC-S to the ocular surface for treatment of severe corneal injuries. Stem Cells Translational Medicine 2019;8:478-489.
严重的角膜损伤常导致永久性视力丧失，仍是临床面临的挑战。人骨髓间充质干细胞（MSCs）及其分泌因子（分泌组）具有抗瘢痕、抗炎和抗血管生成特性，已被研究用于治疗。我们旨在将冻干的 MSC 分泌组（MSC-S）递送至由透明质酸（HA）和硫酸软骨素（CS）组成的粘弹性凝胶中，以此增强角膜再上皮化并减少机械和化学性角膜损伤后的并发症。我们假设与单独使用 MSC-S 或 HA/CS 相比，将 MSC-S 递送至 HA/CS 中会具有更好的伤口愈合效果。结果表明，HA/CS 中的 MSC-S 每日一次的应用可促进角膜损伤后的上皮细胞增殖和伤口愈合。它还减少了碱性角膜烧伤后的瘢痕形成、血管新生和出血。我们发现，MSC-S 和 HA/CS 的组合增加了与 HA 共定位的 CD44 受体的表达，表明 MSC-S 和 HA/CS 之间观察到的治疗效果部分是通过 HA 上调和激活 CD44 受体介导的。这项研究的结果表明，将 MSC-S 递送至眼表面以治疗严重角膜损伤是一种可重复且有效的方法。《干细胞转化医学》2019；8：478-489。
