title: Immediate intraportal transplantation of human bone marrow mesenchymal stem cells prevents death from fulminant hepatic failure in pigs.
abstract: The effectiveness of human bone marrow mesenchymal stem cell (hBMSC) transplantation to treat acute and chronic liver injury has been demonstrated in animal models and in a few nonrandomized clinical trials. However, no studies have investigated hBMSC transplantation in the treatment of fulminant hepatic failure (FHF), especially in large animal (pig) models. The aim of this study was to demonstrate the safety, effectiveness, and underlying mechanism of hBMSC transplantation for treating FHF in pigs through the intraportal route. Human BMSCs (3 × 10(7) ) were transplanted into pigs with FHF via the intraportal route or peripheral vein immediately after D-galactosamine injection, and a sham group underwent intraportal transplantation (IPT) without cells (IPT, peripheral vein transplantation [PVT], and control groups, respectively, n = 15 per group). All of the animals in the PVT and control groups died of FHF within 96 hours. In contrast, 13 of 15 animals in the IPT group achieved long-term survival (>6 months). Immunohistochemistry demonstrated that transplanted hBMSC-derived hepatocytes in surviving animals were widely distributed in the hepatic lobules and the liver parenchyma from weeks 2 to 10. Thirty percent of the hepatocytes were hBMSC-derived. However, the number of transplanted cells decreased significantly at week 15. Only a few single cells were scattered in the regenerated liver lobules at week 20, and the liver tissues exhibited a nearly normal structure.
  
  
  CONCLUSIONS
  Immediate IPT of hBMSCs is a safe and effective treatment for FHF. The transplanted hBMSCs may quickly participate in liver regeneration via proliferation and transdifferentiation into hepatocytes during the initial stage of FHF. This method can possibly be used in future clinical therapy.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Liyuan
authors.initials: L
authors.lastname: Zhang
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Xin
authors.forename: Longyan
authors.initials: L
authors.lastname: Jiang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Linfeng
authors.initials: L
authors.lastname: Jin
authors.forename: Jianzhou
authors.initials: J
authors.lastname: Li
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhou
authors.forename: Shaorui
authors.initials: S
authors.lastname: Hao
authors.forename: Hongcui
authors.initials: H
authors.lastname: Cao
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D006801:Humans; D017114:Liver Failure, Acute / Q000401:mortality* / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D013552:Swine; D013556:Swine, Miniature