title: Prevention of acute liver allograft rejection by IL-10-engineered mesenchymal stem cells.
abstract: 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.
authors: General Surgery of the Hospital Affiliated Xuzhou Medical College, Xuzhou, China.
authors: J
authors: J
authors: Niu
authors: W
authors: W
authors: Yue
authors: Y
authors: Y
authors: Song
authors: Y
authors: Y
authors: Zhang
authors: X
authors: X
authors: Qi
authors: Z
authors: Z
authors: Wang
authors: B
authors: B
authors: Liu
authors: H
authors: H
authors: Shen
authors: X
authors: X
authors: Hu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016753:Interleukin-10
keywords: interleukin-10; liver transplantation; mesenchymal stem cells (MSCs); transplantation tolerance