Stem Cells Transl Med. 2019 Jan 15. doi: 10.1002/sctm.18-0178. [Epub ahead of print]

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

Fernandes-Cunha GM¹, Na KS^1,2, Putra I³, Lee HJ¹, Hull S⁴, Cheng YC¹, Blanco IJ¹, Eslani M³, Djalilian AR³, Myung D^1,4,5.

Abstract

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 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 expression of CD44 receptors co-localized 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.