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Masahiro Omoto, Yiping Jin, Reza Dana, Sunil K. Chauhan; Mesenchymal Stem Cells Suppress Alloimmunity in Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2380. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Bone marrow-derived mesenchymal stem cells (MSC) display a unique anti-inflammatory and immunomodulatory property, and have the potential for treating various immune diseases. The purpose of this study was to investigate the capacity of MSC to suppress induction of alloimmunity in corneal transplantation.
MSC were generated from the bone marrow of GFP-C57BL/6 mice. Corneal grafts from BALB/c (H-2d) mice were transplanted onto C57BL/6 (H-2b) recipient mice. Phenotypically (expression of CD45-CD34-SCA1+CD29+) and functionally (differentiation into adipocytes) characterized MSC (1x106 cells) were intravenously administered to one group of allograft recipients after 2h of transplant surgery. Homing of administered MSC to the corneas was examined at day 3 post-transplantation by immunohistochemistry. Frequencies of IFNγ+ T cells in the draining lymph nodes (LN) were analyzed at day 14 post transplantation using the ELISPOT assay. Frequencies of mature CD11C+MHC-II+ antigen-presenting cells in the corneas and draining LN were analyzed by flow cytometry.
Intravenously injected MSC were found in the transplanted cornea, but not in the normal (contralateral) cornea. The draining LN of MSC-injected allograft recipients showed significantly lower frequencies of the both directly (316±10 vs. 350±17 T cells, p=0.023) and indirectly (42±6 vs. 69±15 T cells, p=0.03) allosensitized IFNγ-secreting T cells compared to the control group. 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.
Our data demonstrating MSC homing to transplanted corneas, and suppression of antigen-presenting cell maturation and induction of alloreactive T cells support the hypothesis that immunomodulatory properties of MSC could be used to prolong corneal allograft survival.
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