Safety and Efficacy of Diverse Mesenchymal Stem Cells Transplantation for Liver Failure

Clinical Comparison of Safety and Efficacy of Allogeneic Umbilical-Cord and Bone Marrow-derived Mesenchymal Stem Cells Transplantation for HBV-related Liver Failure

HBV-related liver failure (HBV-LF), a dramatic clinical syndrome, is characterized with massive necrosis of liver cells. Liver transplantation might be the most effective therapy for HBV-LF. However, there are a lot of problems such as lack of donors, surgical complications, transplant rejection, and high cost, which could limit the application of liver transplantation. It is demonstrated that mesenchymal stem cells could directionally differentiate into hepatocytes and cholangiocytes in injured liver, as well as reduce inflammation of the liver by immune regulation. In this study, we assess the safety and efficacy of human bone marrow and umbilical cord mesenchymal stem cells transplantation for patients with HBV-LF.

Participants will receive conventional treatment plus a dose of BM-MSC(each subgroups with a different dose ) and then be followed until the week 72 study visit.

Participants will receive conventional treatment plus a dose of UC-MSC(each subgroups with a different dose ) and then be followed until the week 72 study visit.

Received conventional treatment and bone marrow mesenchymal stem cells transplantation by peripheral vein slowly for 30minutes. (1×10e5/Kg,1×10e6/Kg,or 1×10e7/Kg, once a week, 8 times).

Received conventional treatment and bone marrow mesenchymal stem cells transplantation by peripheral vein slowly for 30minutes. (1×10e5/Kg,1×10e6/Kg,or 1×10e7/Kg, once a week, 8 times)

Received conventional treatment including: A.antiviral drugs(Entecavir,Lamivudine,Adefovir dipivoxil,et al); B.Hepatoprotective drugs(Ademetionine1,4-butanethiosulfonate for Injection, Reduced Glutathione for Injection,Polyene Phosphatidylcholine, et al); C.Plasma.

The levels of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST),Cholinesterase (CHE) ,Total Bilirubin(TB),Direct Bilirubin(DB), Serum Albumin （ALB）

The improvement of clinical symptoms [including appetite, debilitation, abdominal distension, edema of lower limbs, et al

cluster of differentiation 4 (CD4+)T/ cluster of differentiation 8 (CD8+)T,T helper cell 1 (Th1)/ T helper cell 1(Th2),natural killer cell(NK),natural killer T(NK T),interleukin-1β(IL-1β),interleukin-4(IL-4),interleukin-6(IL-6),interleukin-8(IL-8),interleukin-12(IL-12),interleukin-15(IL-15),interleukin-17A(IL-17A),Tumor necrosis factor-alpha (TNF-α),Interferon-gamma (IFN-γ)

Inclusion Criteria: Aged 18-65 years Liver failure Negative pregnancy test (female patients in fertile age) Written consent HBsAg positive TB≥171 μmol/L or ascend ≥17.1 μmol/L/per day, INR≥1.5 or 20%<PTA≤40% 17≤MELD score≤30 Exclusion Criteria: Hepatocellular carcinoma or other malignancies Severe problems in other vital organs(e.g.the heart,renal or lungs) Pregnant or lactating women Severe bacteria infection Anticipated with difficulty of follow-up observation Liver failure caused by other reasons, such as autoimmune diseases, alcohol, drug and so on Other candidates who are judged to be not applicable to this study by doctors