FTY720 in Corneal Concordant Xenotransplantation

Sedláková, Klára; Muckersie, Elizabeth; Robertson, Marcus; Filipec, Martin; Forrester, John V.

doi:10.1097/01.tp.0000151005.37985.de

Cited by 14 publications

(21 citation statements)

References 44 publications

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“…Rejection was defined as a complete loss of graft transparency (i.e. the pupil margin and iris structure were not visible through the graft) 5 …”

Section: Methodsmentioning

confidence: 99%

“…The pig cornea, which has refractive properties and thickness similar to the human cornea, may be useful for human substitution 1,2 . However, previous studies on corneal xenotransplantation have produced disappointing results with regard to graft survivals; donor corneas are rejected in an acute fashion in 2 days to 2 weeks 3–5 . In fact, our previous studies showed that pig corneas were invariably rejected in rats and mice within 12 days and that the rejected grafts were infiltrated with innate immune cells such as macrophages and neutrophils, as well as T cells 6,7 .…”

Section: Introductionmentioning

confidence: 99%

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

Kim

et al. 2009

Veterinary Ophthalmology

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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. Animals studied Pig and rat. Procedures 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-c 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-c 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.

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“…Rejection was defined as a complete loss of graft transparency (i.e. the pupil margin and iris structure were not visible through the graft) 5 …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Kim

et al. 2009

Veterinary Ophthalmology

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“…2004). Some investigators found (Sedlakova et al. 2005) that intraperitoneal injection of FTY720 could prolong graft survival in rat‐to‐mouse corneal xenografts.…”

Section: Introductionmentioning

confidence: 99%

Systemic application of sphingosine 1‐phosphate receptor 1 immunomodulator inhibits corneal allograft rejection in mice

Zhu

Liu

et al. 2013

Acta Ophthalmologica

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. Purpose: This study aims to investigate the effects of systemic application of sphingosine 1‐phosphate receptor 1(S1P1) on allogeneic corneal transplantation in mice. Methods: A total of 112 BALB/c mice received corneal grafts from C57BL/6 donors. Recipients were randomly divided into seven groups and treated with intraperitoneal injections of S1P1 (5 mg/kg/days), cyclosporine A (5 mg/kg/days), dexamethasone (1 mg/kg/days) and rapamycin (2 mg/kg/days). S1P1was combined with rapamycin or cyclosporine A, and saline served as negative control. Serum levels of IL‐2, IL‐10, TGF‐β1 and IFN‐γ were measured by Elisa. The numbers of CD4+ T and regulatory (Treg) cell phenotype were measured by flow cytometry. Cytokine mRNA expression was analysed by real‐time quantitative PCR. CD4+ T cells and cytokines were histologically identified by immunofluorescence staining. Results: Corneal graft survival was prolonged by intraperitoneal injections in S1P1 alone (mean survival time MST, 35.3 ± 5.6 days), S1P1 combined with rapamycin (MST, 38.7 ± 6.5 days) or S1P1 and cyclosporine A (MST, 32.7 ± 4.8 days) compared with the controls (MST, 14.6 ± 0.2 days; n = 5, p < 0.01). S1P1 alone increased CD4+ T (p < 0.01) and Treg cells (p < 0.01; n = 5) in the cervical and mesenteric lymph nodes compared with the controls and S1P1 + rapamycin (p < 0.05; n = 5). TGF‐β1 and IL‐10 mRNA transcriptions in corneal grafts following S1P1+ rapamycin increased (both p < 0.01; n = 3), and TGF‐β1 and IL‐10 in the serum level following S1P1 alone increased (both p < 0.01; n = 3). These results paralleled the findings obtained from immunofluorescence. Conclusion: S1P1 has significant effect in corneal allograft rejection inhibition. The combined treatment of S1P1 and rapamycin results in synergistic effect.

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“…Many cells are present in the anterior chamber, and significant numbers of lymphocytes and cells of the monocyte/macrophage lineage invade the surrounding tissue and, to a lesser extent, the graft. 3,4 Although mechanisms of xenograft rejection differ from allograft rejection, 5,6 similarities do exist. Hyperacute or acute vascular rejections, described for solid organ xenotransplants, do not occur in this model.…”

mentioning

confidence: 97%

“…One promising agent seems to be FTY720, which substantially suppresses the severity of the inflammatory response and dose-dependently postpones rejection. 4 Because corneal graft rejection involves mainly T cells and macrophages producing NO, [8][9][10] we tested the effects of calcineurin inhibitor cyclosporine A (CsA), monoclonal antibody (mAb) anti-Thy 1.2, and a specific inhibitor of inducible NO synthase (iNOS) on corneal xenograft rejection in 2 groups of recipients. The recipients differ in the type of suturing technique.…”

mentioning

confidence: 99%