Korean J Transplant.  2023 Nov;37(Suppl 1):S31. 10.4285/ATW2023.F-5989.

Addition of SD282 (biguanide derivatives) may attenuate inflammation and improve immune homeostasis in liver transplantation

• Lee SK
• Choi JY
• Park MJ
• Choi JW
• Choi HJ
• You YK
• Jang JW
• Sung PS
• Yoon SK
• Cho ML

• KMID: 2551605
• DOI: http://doi.org/10.4285/ATW2023.F-5989

Abstract

Background
Liver transplantation (LT) is an ultimate treatment in patients with end-stage liver disease. Although tacrolimus reduces the risk of rejection effectively, risks of rejection and long-term side effects, such as chronic renal disease and malignancy, are still unsolved problem in LT patients. In this study, we tried to evaluate the effects of combination treatment with SD282 (biguanide derivatives) and tacrolimus on immune homeostasis in vitro and in vivo mice models.
Methods
T cell proliferation and subtypes after T cell activation or allogeneic stimulation were evaluated in vitro analysis using mouse and human cells by administration of SD282 and tacrolimus. Using graft-versus-host (GVHD) mice model, the severity of GVHD and weight changes were evaluated after administration of SD282 and tacrolimus. The synergistic effects were also evaluated in rat LT model and avatar mouse model using peripheral blood mononuclear cells (PBMCs).
Results
Combination treatment with SD282 and tacrolimus attenuated alloreactive T cell responses in vitro mouse and human cells. In GVHD mice model, combination treatment also reduced the severity of GVHD along with an increase in regulatory T cells. Moreover, in rat LT model demonstrated that the inflammation, fibrosis, and survival was better in the combination treatment. Patient-derived avatar mice model using PBMCs of LT patients also showed a decrease in STAT3 ⁺ T cells along with an increase in FoxP3 ⁺ Treg cells in combination therapy.
Conclusions
This study demonstrated that combination treatment with SD282 and tacrolimus may improve immune homeo-stasis of LT.