Abstract Ocular surface and cornea injuries from exposure to sulfur mustard are one of the main causes of its morbidities. A critical limitation of our current treatment regimens is the inability to promote repair of the cornea during the acute phase and to prevent the long-term complications after sulfur mustard. Therefore, more effective therapies are needed to promote repair of the cornea while also preventing the secondary complications such as fibrosis and neovascularization which lead to significant loss of vision. The main focus of the parent award (Mechanisms of Corneal Epithelial Disease and Repair) is to develop novel therapies to repair the corneal epithelium in pathologic states. This administrative supplement will allow us to expand our current studies in response to the NIH Countermeasures Against Chemical Threats (CounterACT) program to devleop novel therapeutics that can promote corneal repair and prevent/treat the severe corneal complications from exposure to the chemical warfare agent sulfur mustard. Our proposed therapeutics are specifically built around Mesenchymal Stem/Stromal cells (MSCs) and their secreted factors. As part of the studies supported by the parent award, we have been investigating MSCs and have found that they have significant therapeutic potential for promoting corneal repair. MSCs have been shown to possess potent therapeutic effects in other models of ocular surface injury, including enhancing survival, preventing inflammation, scarring and neovascularization of the cornea. Our central hypothesis is that MSCs via their secreted factors can mitigate the ocular surface damage from vesicant agents by enhancing cell survival and further preventing secondary corneal complications. We will pursue the following two specific aims: Aim 1: Determine the effect of Mesenchymal Stromal Cell (MSCs) secreted factors on the immediate cytotoxic effects in the cornea following exposure to nitrogen mustard in vitro and ex vivo. Aim 2. Investigate the effect of MSCs and MSC secreted factors on preventing the delayed pathologic responses in the cornea following chemical nitrogen mustard injury in vivo. These studies will facilitate the development of novel MSC-based therapies to prevent the immediate and chronic pathologic changes in the cornea following sulfur mustard injury.