Dual Treatment of CD40 Silencing or Mesenchymal Stem Cells Infusion with Sub-Therapeutic Doses of Cyclosporine Effectively Prevents Acute Rejection in an Allogenic Model of Renal Transplantation

J. Guiteras¹, L. De Ramon¹, N. Bolaños¹, M. Franquesa², M. Gomà³, J. Cruzado⁴, N. Lloberas¹, J. Grinyó⁴, J. Torras⁴

¹IDIBELL, Hospitalet de Llobregat, Spain, ²IGTP, Badalona, Spain, ³Bellvitge Hospital, Hospitalet de Llobregat, Spain, ⁴Bellvitge Hospital / IDIBELL, Hospitalet de Llobregat, Spain

Meeting: 2019 American Transplant Congress

Abstract number: A12

Keywords: Calcineurin, Co-stimulation, Rejection, Stem cells

Session Information

Session Name: Poster Session A: Acute Rejection

Session Type: Poster Session

Date: Saturday, June 1, 2019

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

*Purpose: This study was designed to investigate the combination of CD40 silencing or MSC infusion with suboptimal doses of Cyclosporine in this renal allograft model.

*Methods: In this model, rats were randomly allocated into different groups: Non-Treated (n=10); Scrambled siRNA (n=10); Cyclosporine (control full dose, 5 mg/kg/day) (n=9); CsA1/2 (sub-therapeutic, 2.5 mg/kg), (n=5); MSC, group treated with two MSC doses at day -7 and day 0 (n=8); siRNA-CD40 (500 μg), (n=5); CsA1/2+siRNA-CD40 group (n=5) and CsA1/2+MSC group (n=8). Heterotopic renal transplantation was performed from Wistar to Lewis rats, with 21 days of follow up. Survival, renal function, conventional histology and immunohistochemistry (CD68 cells, CD3 cells, glomerular and peritubular capillary C4d) were analyzed in all groups.

*Results: Monotherapy either with CsA1/2, siRNA-CD40 or MSC showed slight improvement in all the studied parameters compared with Non-treated or Scrambled groups. The combined therapy using CsA1/2+MSC or CsA1/2+siRNA-CD40 displayed significant amelioration of these parameters compared to monotherapy groups. Interestingly, the CsA1/2+siRNA-CD40 group presented a clear reduction of glomerular and peritubular C4d deposition and the degree of CD3 infiltrate, reaching similar values to Cyclosporine full dose group.

*Conclusions: In conclusion, siRNA or MSC combined with sub-therapeutic doses of Cyclosporine offered better prevention in allograft rejection and survival than monotherapy groups. But was the CsA1/2+siRNA-CD40 group that gave the greatest prevention both in the cellular and humoral arms, perhaps by an additive effect.

To cite this abstract in AMA style:

Guiteras J, Ramon LDe, Bolaños N, Franquesa M, Gomà M, Cruzado J, Lloberas N, Grinyó J, Torras J. Dual Treatment of CD40 Silencing or Mesenchymal Stem Cells Infusion with Sub-Therapeutic Doses of Cyclosporine Effectively Prevents Acute Rejection in an Allogenic Model of Renal Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/dual-treatment-of-cd40-silencing-or-mesenchymal-stem-cells-infusion-with-sub-therapeutic-doses-of-cyclosporine-effectively-prevents-acute-rejection-in-an-allogenic-model-of-renal-transplantation/. Accessed November 24, 2024.

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