Combined therapy of mesenchymal stem cell transplantation and interleukin 1 receptor antagonist for swine acute liver failure

Abstract

Objective To evaluate synergic effects of allogeneic mesenchymal stem cells (MSCs) transplantation and interleukin 1 receptor antagonist (IL-1Ra) on swine acute liver failure.Methods Chinese experimental mini swine were given D-galactosamine to establish models of acute liver failure.Twentyone pigs were randomly divided into three groups (n =7 each).In the control group (A),the normal saline was injected into the liver via the portal vein after induction for 24 h; In the MSCs transplantation group (B),8 × 107 MSCs (in 40 ml PBS) were injected into the liver via the portal vein after induction for 24 h;In combined therapy group (C),8 × 107 MSCs were injected into the liver via the portal vein after induction for 24 h,followed by injection of rhIL-1Ra (10 mg/pig) via the ear vein at 6 h before,and one day and three days after transplantation respectively.Liver function,serum inflammation and pathological changes were measured.The fate of MSCs was also observed.Results The biochemical assay,the serum inflammation level and pathological changes in group C were all greatly different from those in group A and group B (P ＜ 0.05).The proliferation rate of hepatocytes in group C was 67.70 ± 9.47,71.80 ± 9.45,and 40.04 ±4.60 one week after transplantation,significantly higher than in group A and group B (P ＜ 0.05).The number of MSCs in group C was greater than in group B.Hepatocytes regeneration were associated with the kinesis changes of inflammation.Our findings suggest IL-1 Ra as an important player in the repair of acute liver failure (ALF).Improving homeostasis of liver failure contributed to increased hepatic engraftment and hepatocytes proliferation.Conclusion The MSCs transplantation is useful for ALF partially.The combined therapy shows cooperative effects. Key words: Interleukin 1 receptor antagonist ; Mesenchymal stem cells ; Cell transplantation ; Acute liver failure