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Masahiro Omoto, Yiping Jin, Sunil Chauhan; Host Mesenchymal Stem Cells Home to Transplanted Cornea and Promote Allograft Survival. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2056.
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Along with their capacity for differentiating into cells of multiple lineages, mesenchymal stem cells (MSC) have generated great interest for their ability to display unique anti-inflammatory and immunomodulatory properties. The purpose of this study was to investigate whether systemically-injected host MSC can home to the inflamed transplanted cornea, suppress induction of alloimmunity, and promote allograft survival rate.
MSC (CD45-CD34-SCA1+CD29+) were generated from the bone marrow of wild-type BALB/c or GFP+ C57BL/6 mice, and 1x106 cells were intravenously injected to allografted recipients 2h after surgery. To track the homing of GFP+ MSC (C57BL/6), corneal grafts from BALB/c (H-2d) mice were transplanted onto C57BL/6 (H-2b) recipient mice. MSC homing to the corneas was examined at day 3 post-transplantation by immunohistochemistry. To investigate the effect of MSC on alloimmunity and graft survival, corneal grafts from C57BL/6 (H-2b) mice were transplanted onto BALB/c (H-2d) recipient mice, and then wild-type BALB/c MSC were injected. Frequencies of alloreactive IFNγ+ T cells were analyzed at day 14 post-transplantation using the ELISPOT assay. Frequencies of mature CD11C+MHC-II+ antigen-presenting cells were analyzed by flow cytometry. Graft survival was evaluated by slit-lamp biomicroscopy weekly up to 8 weeks.
Intravenously injected GFP+MSC were found in abundance in the transplanted cornea, but not in the ungrafted (contralateral) cornea. The frequencies of mature CD11C+MHC-II+ antigen-presenting cells were substantially decreased in the corneas (50.2% vs. 76.7%) and draining lymph nodes (4.4% vs. 8.4%) of MSC-injected allograft recipients compared to control group. The draining LN of MSC-injected allograft recipients showed significantly lower frequencies allosensitized IFNγ-secreting T cells compared to the control group (p=0.023). Allograft survival rate was significantly (~2-fold) higher (p = 0.03) in the MSC-injected recipients (80%, n=12) compared to the non-MSC injected group (40%, n =10).
Our data demonstrate that systemically-administered MSC specifically home to transplanted corneas and promote allograft survival by inhibiting APC maturation and induction of alloreactive T cells. These data suggest that host MSC exert immunomodulatory functions in corneal transplantation and may be used to prolong transplant survival.
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