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


METHODS
Pig and rat.


METHODS
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.
Oh
Joo Youn
JY
Department of Ophthalmology, Seoul National University College of Medicine, 28 Yeongeon-dong, Chongno-gu, Seoul 110-744, Korea.
Kim
Mee Kum
MK
Ko
Jung Hwa
JH
Lee
Hyun Ju
HJ
Lee
Jin Hak
JH
Wee
Won Ryang
WR
D000818:Animals; D016039:Corneal Transplantation / Q000662:veterinary*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D008297:Male; D059630:Mesenchymal Stem Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
D016207:Cytokines