Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cordderived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:725-731

Background and Aim: Ursodeoxycholic acid (UDCA) treatment is an effective medical therapy for patients with primary biliary cirrhosis (PBC); however, 40% of PBC patients show an incomplete response to the UDCA therapy. This study aimed to investigate the safety and efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transfusion in PBC patients with an incomplete response to UDCA. Methods: We conducted a single-arm trial that included seven PBC patients with a suboptimal response to UDCA treatment. UC-MSCs were first cultured, and then 0.5 ¥ 10

Our results suggest that TNF-alpha plays a critical role in the development of brain oedema in ALF, and that both vasogenic and cytotoxic mechanisms may be involved. Increased BBB permeability may be because of the disruption of TJs, and loss of the TJ-associated protein occludin.

There is increasing interest in the role of T follicular helper (Tfh) cells in autoimmunity from the perspective of both their role in breach of tolerance and their effects on the natural history of disease progression. Indeed, the critical role of Tfh cells in autoimmunity is further highlighted based on their location in the germinal center (GC), a pathogenic hot spot for development of autoreactivity. To address the role of Tfh cells in primary biliary cirrhosis (PBC), we comprehensively evaluated the immunobiology of CXCR5+CD4+ Tfh cells in 69 patients with PBC, including a nested subgroup of 16 autoimmune hepatitis (AIH) and 20 healthy controls (HC), followed for one year. We report herein several key observations. Firstly, there was an increased frequency of circulating Tfh cells in patients with PBC compared to AIH (p < 0.05) and HC (p < 0.01). Second, the function of circulating Tfh cells from PBC patients, including IL-21 production (p < 0.05), the ability to promote B cell maturation and autoantibody production, were greater than HC. Third, the frequency of these cells was significantly decreased in UDCA responders compared to UDCA-treated non-responders, in both cross-sectional (p = 0.023) and longitudinal studies (p = 0.036),respectively. Indeed, similar increases of Tfh cells were noted in liver and spleen. In conclusion, these results significantly extend our understanding of lymphoid subpopulations in PBC and their relative role in disease expression. Our data also provide a novel biomarker for evaluation of the effectiveness of new therapeutic approaches.

Nanoscale Ag semishell arrays with controlled size and tunable interparticle distance were prepared by combining nanosphere lithography with reactive ion etching. First, a large-area ordered monolayer of polystyrene (PS) nanospheres was deposited on glass substrates using the Langmuir−Blodgett (LB) technique. The PS spheres with different diameters were employed in LB procedures. Second, the monolayers of PS spheres were etched to control the diameter and tune the interparticle distance. Finally, a Ag layer was evaporated on the etched PS templates. Ag films with periodical nanostructures were obtained and can be used as surface-enhanced Raman scattering (SERS) substrates. These substrates exhibited homogeneity and good enhancement ability. SERS enhancement factor (EF) was represented on the order of 104−105. The correlation between nanoscale morphology and SERS activity of the substrates was investigated. When the size of Ag-semishell was fixed, the EF value decreased with the increase of interparitcle distance. Both local surface plasmon mode and delocalized surface plasmon mode contributed to the total enhancement. The controlled size, tunable interparticle distance, and large-area ordered arrays of these substrates suggest their promising applications as functional components in spectroscopy, immunoassay, biosensors, and biochips.

The purpose of this study was to characterize the changes in metabolic intermediates and to investigate the metabolic profile of a mouse model of fulminant hepatic failure (FHF), induced by D-galactosamine/lipopolysaccharide (GalN/LPS). Plasma metabolite levels were detected using gas chromatography/time-of-flight mass spectrometry, and the acquired data were transferred into Simca-P and processed using principal components analysis (PCA). In total, 45 metabolites were identified from the 267 distinct compounds found in the study. Whereas significant differences were noted in the plasma levels of the control and FHF groups, no differences in gluconeogenesis or glycolysis were noted following GalN/LPS treatment. Our data also suggest that the production of ketone bodies, and the tricarboxylic acid and urea cycles, was inhibited. PCA data suggest that 5-hydroxyindoleacetic acid, glucose, beta-hydroxybutyrate, and phosphate parameters had the highest weights on each of the principal components, and that they were the most important metabolites contributing to the separation of groups. In conclusion, this metabonomic approach can be used as a powerful tool to characterize changes in metabolic intermediates and to search for metabolic markers under certain pathophysiological conditions, such as FHF. Our data also demonstrate that a combination of 5-hydroxyindoleacetic acid, glucose, beta-hydroxybutyrate, and phosphate concentrations in the plasma is a potential marker for FHF, as well as for the early prognosis of FHF.

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