Mesenchymal stem cells home to inflamed ocular surface and suppress allosensitization in corneal transplantation.

PURPOSE: To investigate whether systemically injected syngeneic mesenchymal stem cells (MSCs) can home to the transplanted cornea, suppress induction of alloimmunity, and promote allograft survival.

METHODS: Mesenchymal stem cells were generated from bone marrow of wild-type BALB/c or GFP (green fluorescent protein)+ C57BL/6 mice, and 1×10(6) cells were intravenously injected to allografted recipients 3 hours after surgery. Mesenchymal stem cells homing to the cornea were examined at day 3 post transplantation by immunohistochemistry. MHC (major histocompatibility complex) II+CD11c+ cells were detected in the cornea and lymph nodes (LNs) 14 days post transplantation using flow cytometry. Cytokine expression of bone marrow-derived dendritic cells (BMDCs) was determined using real-time PCR. ELISPOT assay was used to assess indirect and direct host T cell allosensitization, and graft survival was evaluated by slit-lamp biomicroscopy weekly up to 8 weeks.

RESULTS: Intravenously injected GFP+ MSCs were found in abundance in the transplanted cornea, conjunctiva, and LNs, but not in the ungrafted (contralateral) tissue. The frequencies of mature MHC II+CD11c+ antigen-presenting cells (APCs) were substantially decreased in the corneas and draining LNs of MSC-injected allograft recipients compared to control recipients. Maturation and function of in vitro cultured BMDCs were decreased when cocultured with MSCs. Draining LNs of MSC-injected allograft recipients showed lower frequencies of IFNγ-secreting Th1 cells compared to the control group. Allograft survival rate was significantly higher in MSC-injected recipients compared to non-MSC-injected recipients.

CONCLUSIONS: Our data demonstrate that systemically administered MSCs specifically home to the inflamed ocular surface and promote allograft survival by inhibiting APC maturation and induction of alloreactive T cells.