Rat allogeneic mesenchymal stem cells did not prolong the survival of corneal xenograft in a pig-to-rat model

Abstract

Objective Recent reports have demonstrated that mesenchymal stem cells (MSCs) can modulate/suppress immunologic responses through interactions with different immune cells. We performed this study in order to investigate the immunomodulatory effects of MSCs in corneal xenotransplantation. Animals studied Pig and rat. Procedures We orthotopically transplanted pig corneas into rats and topically applied allogeneic rat MSCs to the corneas for 2 h immediately after transplantation. Graft survival was clinically assessed using slit-lamp biomicroscopy and the median survival time (MST) was calculated. The rejected grafts were histologically examined using antibodies against CD4, CD8, CD161, and CD68. The expression of IL-2, IL-6, IL-10, and IFN-gamma was also evaluated in the rejected grafts using an enzyme-linked immunosorbent assay. Results The survival of corneal xenografts was not significantly prolonged by MSC application (MST 10.5 days) compared with the controls (MST 9.67 days) (P = 0.4189). Histologically, the rejected grafts in both groups were massively infiltrated with neutrophils and macrophages. Some CD8+ T cells and rare NK cells were found in the rejected grafts. The levels of IL-6 and IL-10 were significantly increased in the rejected grafts from MSC-treated rats compared with the grafts from MSC-untreated rats. However, the levels of IL-2 and IFN-gamma were not different between the two groups. Conclusions Topical application of allogeneic rat MSCs was ineffective in prolonging corneal xenograft survival in a pig-to-rat model.