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Yiping Jin, Yinan Lan, Hyunsoo Lee, Sunil Chauhan; Effect of Mesenchymal Stem Cells on Corneal Allograft Survival. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1139.
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Bone marrow-derived mesenchymal stem cells (MSC) have generated great interest for their ability to display a unique anti-inflammatory immunomodulatory property. MSC have immense potential for treating various diseases, especially those related to tissue damage involving immune reactions. The purpose of this study was to investigate whether MSC-mediated immunoregulation can prolong the corneal allograft survival.
MSC were generated from the bone marrow of B6 mice. Phenotypically (expression of CD45-CD34-SCA1+CD29+) and functionally (differentiation into adipocytes) characterized MSC were used for both in vitro and in vivo assays. Immunoregulatory effect of MSC on CD3-mAb-mediated proliferation of both naïve and effector (allograft-primed) T cells were investigated in an in vitro co-culture assay using BrdU incorporation method. In addition, effect of MSC on expansion of CD4+Foxp3+ regulatory T cells (Tregs) was investigated using flow cytometry. To investigate effect of MSC on corneal allograft survival, BALB/c grafts were transplanted onto B6 recipients, and then after 24h, MSC (106) were intravenously injected to B6 recipients. Grafts were evaluated using slit-lamp microscopy at weekly intervals up to 8 weeks.
In MSC and T cell co-culture assay, there was significant suppression of CD3-Ab mediated proliferation of both naïve (22 ± 0.4%) and effector (24 ± 1.4%) T cells compared to the proliferation of CD3-Ab mediated T cells alone (P<0.05). In addition, the percentage of CD4+Foxp3+Treg population was increased when T cells were co-cultured with MSC (6.17%) compared to without MSC (3.12%). The corneal allograft rejection rate was significantly delayed in the recipients who received one dose of MSC injection post-operation compared to the allograft recipient without injection of MSC. The graft survival ratios in the MSC injection group were 50% (week2), 16.5% (week3) and 0% (week 4) respectively, while the graft survival ratios in non-MSC group were 14.3% (week2) and 0% (week3) respectively.
Our data suggest that MSC have potential to prolong the corneal allograft survival. MSC-mediated suppression of naïve and effector T cell activation, and expansion of Tregs could be the possible mechanisms involved in the regulation of alloimmunity.
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