title: Augmenter of liver regeneration improves therapeutic effect of hepatocyte homotransplantation in acute liver failure rats.
abstract: Hepatocyte transplantation (HCT) is an available option on treatment for acute liver failure (ALF). However, short-term survival of engraftment and immunological rejections of recipient are major obstacles. Augmenter of liver regeneration (ALR) has cytoprotective and immunoregulatory effects in liver injury, and has been used in many experimental applications. In the present study, we investigated the potential effect and mechanism of recombinant human ALR (rhALR) on ALF rats treated with intraperitoneal HCT. ALF rats induced by d-galactosamine (GalN) were studied in vivo, and were intraperitoneal injected with or without hepatocytes and rhALR 24h after the induction. Animal survival, serum and ascites liver enzymes, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed. Histological examination was performed, and liver regeneration, apoptosis and immunological responses were identified by immunohistochemistry assay. Our results showed that rhALR promoted hepatocytes regeneration, attenuated liver injury and suppressed immunological responses. The ascites liver enzyme, serum and ascites pro-inflammatory cytokines (TNF-α, IL-1β), liver histological injury, apoptotic hepatocytes and activated immunocytes were significantly reduced in ALF rats treated with rhALR and HCT compared with those without rhALR. The proliferative and mitotic hepatocytes were markedly increased, and overall survival improved with rhALR. The administration of rhALR improved survival and promoted liver recovery in HCT treatment for ALF, which was associated with the role of proliferative promoter and immunosuppressor. This study suggests that co-treated with rhALR and HCT can provide a promising strategy for the treatment of ALF.
authors: Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education of China, The Second Affiliated Hospital, Chongqing Medical University, 74 Linjiang Road, Chongqing, 400010, China.
authors: Na
authors: N
authors: Wang
authors: Zhiyi
authors: Z
authors: Wang
authors: Hang
authors: H
authors: Sun
authors: Xiaofeng
authors: X
authors: Shi
authors: Yan
authors: Y
authors: Zhang
authors: Qi
authors: Q
authors: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation; D002478:Cells, Cultured; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007165:Immunosuppression Therapy; D053583:Interleukin-1beta / Q000378:metabolism; D017114:Liver Failure, Acute / Q000628:therapy*; D011506:Proteins / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors
chemical_list: D053583:Interleukin-1beta; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C088825:GFER protein, rat; D050862:Oxidoreductases Acting on Sulfur Group Donors