USE OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS TO TREAT CORNEAL INJURY AND INFECTION

Maintenance of corneal transparency is imperative for vision, as more than two-thirds of the eye’s optical refractive power can be attributed to the cornea. An important tissue within the cornea is the corneal stroma, which accounts for 90% of corneal thickness and which is composed of interwoven collagen fibrils, proteoglycans, and sparsely distributed keratocytes. The lattice arrangement and spacing of the collagen fibrils in the stroma allows for transparency, permitting light to refract through the stroma correctly. Disruption of the collagen fibril architecture through conditions such as corneal injury, bacterial infection, and complications from surgical interventions such as LASIK, can lead to increased corneal opacity and a loss in vision acuity. While previous work in our lab has focused on developing an understanding of the role of Collagen V in the collagen fibril architecture, this project aims to translate this learning into insight on how to efficaciously aid in corneal repair made necessary by injury and infection. Prior findings have shown that human umbilical cord mesenchymal stem cells (hUMSCs) have been able to partially rescue the thin, cloudy corneas of collagen V-null mice with little to no immune rejection or inflammation. Our hypothesis was that hUMSCs would similarly improve corneal opacity brought about by corneal injury and bacterial keratitis infection. Wildtype C57BL/6 mice were used to create two study groups. The first group was used to model corneal injury and received bilateral keratectomies in which a 2 mm in diameter section of corneal epithelium and anterior corneal stroma was removed. The second group modeled corneal infection and was bilaterally infected with Pseudomonas aeruginosa (strain PA01). Mice in each group were subsequently treated on one eye with hUMSCs applied in the form of a stem-cell-rich fibrin gel applied directly to the corneal surface. Corneal opacity was then assessed in these eyes and in contralateral controls that did not receive stem cell treatment using the Heidelberg Retinal Tomograph. Our results indicate that among eyes that underwent keratectomy, hUMSC-treated eyes had significantly reduced corneal opacity as compared to their contralateral controls. Similarly, infected eyes treated with stem cells show a reduction in opacification as compared to non-treated, infected eyes. These results implicate the efficacy of using hUMSCs in treating acquired corneal disease and have led to further, ongoing experimentation in assessing the hUMSC immunomodulatory response in bacterial infection.