Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier

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