Prevention of acute liver allograft rejection by IL‐10‐engineered mesenchymal stem cells

Hepatic allograft rejection remains a challenging problem, with acute rejection episode as the major barrier for long‐term survival in liver transplant recipients. To explore a strategy to prevent allograft rejection, we hypothesized that mesenchymal stem cells (MSCs) genetically engineered with interleukin‐10 (IL‐10) could produce beneficial effects on orthotopic liver transplantation (OLT) in the experimental rat model. Syngeneic MSCs transduced with IL‐10 were delivered via the right jugular vein 30 min post‐orthotopic transplantation in the rat model. To evaluate liver morphology and measure cytokine concentration, the blood and liver samples from each animal group were collected at different time‐points (3, 5 and 7 days) post‐transplantation. The mean survival time of the rats treated with MSCs–IL‐10 was shown to be much longer than those treated with saline. According to Banff scheme grading, the saline group scores increased significantly compared with those in the MSCs–IL‐10 group. Retinoid acid receptor‐related orphan receptor gamma t (RORγt) expression was more increased in the saline group compared to those in the MSCs–IL‐10 group in a time‐dependent manner; forkhead box protein 3 (FoxP3) expression also decreased significantly in the saline group compared with those in the MSCs–IL‐10 group in a time‐dependent manner. The expression of cytokines [IL‐17, IL‐23, IL‐6, interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α] in the saline groups increased significantly compared with the time‐point‐matched MSCs–IL‐10 group, whereas cytokine expression of (IL‐10, TGF‐β1) was deceased markedly compared to that in the MSCs–IL‐10 group. These results suggest a potential role for IL‐10‐engineered MSC therapy to overcome clinical liver transplantation rejection.