Therapeutic efficacy of different routes of mesenchymal stem cell administration in corneal injury

Abstract

PurposeCorneal injuries are associated with significant impairment in vision. Mesenchymal stem cells (MSCs) have been shown to limit inflammation and promote tissue repair at the ocular surface. Here, we evaluate the efficacies of different modes of MSC delivery (topical, subconjunctival, intraperitoneal [IP] and intravenous [IV]) to promote tissue repair and restore corneal transparency in a murine model of corneal injury. MethodsMSCs were purified from the bone marrow of C57BL/6 mice and expanded using plastic adherence in vitro. Corneal injury was created using an Algerbrush, and 0.5 × 106 MSCs/mouse were administered via topical, subconjunctival, IP or IV routes. Qdot-labeled MSCs were employed to determine the effect of route of administration on corneal and conjunctival MSC frequencies. Corneal opacity scores were calculated using ImageJ. Expression of inflammatory cytokines was quantified by qPCR, and infiltration of CD45+ cells was evaluated by flow cytometry. ResultsSubconjunctival or IV administration results in increased frequencies of MSCs in ocular surface tissues following corneal injury, relative to topical or intraperitoneal delivery. Subconjunctival or IV administration reduces: (i) corneal opacity, (ii) tissue fibrosis as quantified by α-Sma expression, (iii) the expression of inflammatory cytokines (Il-1β and Tnf-α) and (iv) CD45+ inflammatory cell infiltration relative to untreated injured control animals. Administration via subconjunctival or IV routes was observed to accelerate corneal repair by restoring tissue architecture and epithelial integrity. ConclusionsOur data suggest that subconjunctival or IV delivery of MSCs has superior therapeutic efficacy compared to topical or IP delivery following corneal injury.