依维莫司联合间充质干细胞对大鼠肝移植排斥模型中调节性 T 细胞水平的影响。
Effect of the Combination of Everolimus and Mesenchymal Stromal Cells on Regulatory T Cells Levels and in a Liver Transplant Rejection Model in Rats.
机构信息
Department of Abdominal Surgery and Transplantation, University of Liege Hospital [Centre Hospitalier Universitaire (CHU) ULiege], Liege, Belgium.
Centre de Recherche et de Développement du Département de Chirurgie (CREDEC), Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), Cardiovascular Sciences, University of Liege (ULiege), Liege, Belgium.
出版信息
Front Immunol. 2022 Jun 10;13:877953. doi: 10.3389/fimmu.2022.877953. eCollection 2022.
INTRODUCTION
Mesenchymal stromal cells (MSCs) have particular properties that are of interest in organ transplantation, including the expansion of regulatory T cells (Tregs), a key factor in transplant tolerance induction. However, the most effective immunosuppressive drug to associate with MSCs has yet to be defined. Additionally, the impact of the association of everolimus with MSCs on Treg expansion, and on the induction of liver graft tolerance, has never been studied. The aim of this study was to evaluate the effects of MSCs in combination, or not, with everolimus on Treg expansion and in a model of rejection after liver transplantation (LT) in the rat.
METHODS
Firstly, 24 Lewis rats were assigned to 4 groups (n=6 in each group) receiving intravenous MSCs or saline injection at day (D)9 with/without subcutaneous everolimus from D0 to D14. Analysis of circulating Tregs was performed at D0, D14 and D28. In a second set of experiment, 30 Lewis rats were randomized in 3 groups 48hours after LT with a Dark Agouti rat liver: everolimus (subcutaneous for 14 days), MSCs (intravenous injection at post-operative day 2 and 9), or both everolimus and MSCs. Rejection of the liver graft was assessed by liver tests, histology and survival.
RESULTS
Individually, MSC infusion and everolimus promoted Treg expansion in rats, and everolimus had no negative impact on Treg expansion in combination with MSCs. However, in the LT model, injections of MSCs two and nine days following LT were not effective at preventing acute rejection, and the combination of MSCs with everolimus failed to show any synergistic effect when compared to everolimus alone.
CONCLUSION
Everolimus may be used in association with MSCs. However, in our model of LT in the rat, post-transplant MSC injections did not prevent acute rejection, and the association of MSCs with everolimus did not show any synergistic effect.
简介
间充质基质细胞（MSCs）具有特殊的特性，在器官移植中很有意义，包括调节性 T 细胞（Tregs）的扩增，这是诱导移植耐受的关键因素。然而，与 MSCs 相关联的最有效的免疫抑制药物尚未确定。此外，everolimus 与 MSCs 联合应用对 Treg 扩增以及诱导肝移植（LT）后肝移植物耐受的影响尚未被研究。本研究旨在评估 MSCs 与 everolimus 联合或不联合应用对 Treg 扩增的影响，并在大鼠 LT 后排斥反应模型中进行研究。
方法
首先，将 24 只 Lewis 大鼠随机分为 4 组（每组 6 只），分别于第 9 天（D）静脉注射 MSCs 或生理盐水，并于第 0 天至第 14 天皮下注射 everolimus。在 D0、D14 和 D28 时分析循环 Treg。在第二组实验中，30 只 Lewis 大鼠在 LT 后 48 小时随机分为 3 组，接受 Dark Agouti 大鼠肝：everolimus（皮下注射 14 天）、MSCs（术后第 2 天和第 9 天静脉注射）或 everolimus 和 MSCs 联合应用。通过肝功能试验、组织学和生存评估评估肝移植物的排斥反应。
结果
单独应用 MSC 输注和 everolimus 可促进大鼠 Treg 扩增，而 everolimus 与 MSCs 联合应用时对 Treg 扩增无负面影响。然而，在 LT 模型中，LT 后第 2 天和第 9 天注射 MSCs 并不能有效预防急性排斥反应，与单独使用 everolimus 相比，MSCs 与 everolimus 联合应用也没有显示出任何协同作用。
结论
everolimus 可与 MSCs 联合应用。然而，在我们的大鼠 LT 模型中，移植后 MSC 注射不能预防急性排斥反应，MSCs 与 everolimus 联合应用也没有显示出任何协同作用。
Zotero 插件