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Mesenchymal stromal cells combined with everolimus promote Treg expansion but do not synergize in a rat liver transplant rejection model
VANDERMEULEN, Morgan; ERPICUM, Pauline; BLETARD, Noëlla et al.
2021In Transplant International, 34 (S1 OP519), p. 101
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Abstract :
[en] Background: Mesenchymal stromal cells (MSCs) have particular properties that can be of interest in organ transplantation, including expansion of regulatory T cells (Tregs), a key factor in graft tolerance induction. The immunosuppression to be associated with MSCs has not yet been defined. Additionally, the impact of the association of everolimus with MSCs on Treg expansion and on induction of liver graft tolerance has never been studied. The aim of this study was to evaluate the effects of MSCs combined, or not, with everolimus, on Treg expansion and in a model of liver transplantation (LT) rejection in the rat. Methods: Firstly, Lewis rats received intravenous MSCs at D9 with/without subcutaneous everolimus from D0 to D14. Analysis of circulating Tregs was performed at D0, D14 and D28. Secondly, 48 h after LT with a Dark Agouti rat liver, 30 Lewis rats were randomized in 3 groups: everolimus (subcutaneous for 14 days), MSCs (intravenous injection at D2 and D9), 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 when combined with MSCs. However, in the LT model, injections of MSCs 2 and 9 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.
Disciplines :
Gastroenterology & hepatology
Surgery
Author, co-author :
VANDERMEULEN, Morgan ;  Centre Hospitalier Universitaire de Liège - CHU > Département de chirurgie > Chirurgie abdo, sénologique, endocrine et de transplantation
ERPICUM, Pauline ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
BLETARD, Noëlla ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service d'anatomie et cytologie pathologiques
POMA, Laurence ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
Drion, Pierre ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Méth. expér. des anim. de labo et éthique en expér. anim.
JOURET, François  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
DETRY, Olivier  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de chirurgie > Chirurgie abdo, sénologique, endocrine et de transplantation
Language :
English
Title :
Mesenchymal stromal cells combined with everolimus promote Treg expansion but do not synergize in a rat liver transplant rejection model
Publication date :
August 2021
Event name :
ESOT 2021
Event organizer :
European Society of Transplantation
Event place :
Milan, Italy
Event date :
Du 29 aout au 1 septembre 2021
Audience :
International
Journal title :
Transplant International
ISSN :
0934-0874
eISSN :
1432-2277
Publisher :
Blackwell, Oxford, United Kingdom
Volume :
34
Issue :
S1 OP519
Pages :
101
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 29 September 2021

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