Abstract
Purpose :
Mesenchymal Stromal/Stem Cells (MSCs) play an important role in tissue repair and maintenance and have been used as cell therapy in numerous clinical studies. In this study, we aim to investigate whether bone marrow-derived mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) could regulate corneal epithelial wound healing. We investigated the therapeutic potential of MSC-Exos after corneal epithelial injury and test the functional stability and clinical applicability of lyophilized MSC-conditioned media (MSC-CM) and MSC-Exos for the treatment of corneal epithelial wounds.
Methods :
Conditioned media was collected from passage 4 human bone marrow MSC. Primary human corneal epithelial cells and human corneal limbal epithelial cell lines and mouse eyes after 2mm-diameter corneal epithelial wounds. The effect of MSC secretome/exosomes on cell viability, cytotoxicity, endotoxin, and cell proliferation was investigated. The dose-dependent effects on corneal wound repair and the effects of freeze-dried CM (reconstituted CM) on wound healing were also studied.
Results :
Human MSC-CM had a low level of cytotoxicity and endotoxin, and resulted in cell survival and cell proliferation. In vivo experiments confirmed that MSC-CM promoted corneal wound healing, whereas exosome-depleted MSC-CM had significantly slower wound healing. Likewise, treatment with exosome-depleted MSC-CM resulted in more corneal fluorescein staining and increased corneal haze/edema relative to exosomes containing MSC-CM. Freeze-dried-CM (reconstituted-CM) stored at 4 degrees was stable for up to 4 weeks without significantly reducing wound healing effects in an in vitro scratch model.
Conclusions :
Taken together, these studies identify MSC-Exos as the active ingredient in MSC-CM that promotes epithelial cell migration and proliferation, resulting in wound-healing effects in the corneal epithelium. MSC-CM-derived exosomes have therapeutic potential and could be helpful in the development of targeted therapies in the cornea.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.