Induction of Mesenchymal to Epithelial Transition of Circulating Mesenchymal Stem Cells by Conditioned Medium of Injured Cornea

We previously reported that substance-P (SP) mobilized mesenchymal stem cells (MSCSP) from bone marrow and recruited them to the injured site, which then participated in wound healing process by incorporation into the corneal epithelium in a rabbit alkali burn model. In the present study, we investigated if the injured microenvironment could stimulate the recruited MSCSP to lose their mesenchymal phenotype and then acquire epithelial phenotype or not. Especially, we focused on the effects of secreted soluble tissue factors of wound microenvironment in the rat cornea wound model. Priming the circulating MSCSP with conditioned medium of the injured tissue at day 5 elicited morphological and molecular changes similar to those noted during mesenchymal to epithelial transition (MET), which was accompanied by the reduction of alpha-smooth muscle actin (alpha-SMA), a typical mesenchymal marker, and induction of E-cadherin, a typical epithelial marker. Furthermore, these primed MSCSP rearranged their actin cytoskeletal system from distinct actin stress fiber projection to the cell-to-cell-contact-enriched actin microfilament. The primed cells also had increased survival in keratinocyte growth medium (KGM). In conclusion, MSCSP could be differentiated in vitro to the epithelial cells under the injured microenvironment, which may also occur in vivo during tissue repair.