A novel treatment regimen for acute liver failure based on a combination of mesenchymal stem cells transplantation and IL-lRa-loaded chitosan nanoparticles / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate whether a combination therapy using allogeneic mesenchymal stem cell (MSC) transplantation and interleukin-1 receptor antagonist (IL-1Ra) chitosan nanoparticles is more robust than MSC transplantation alone for treating acute liver failure and to investigate the mechanisms of the improved therapeutic effect using a swine model system.</p><p><b>METHODS</b>IL-1Ra-loaded nanoparticles were made of lactosylated chitosan-FITC using the electrostatic spray method and analyzed by enzyme-linked immunosorbent assay. The active live targeting of these nanopaticles were investigated by fluorescence microscope and flow cytometer(FCM). The combined therapy was given and the Detailed Steps as follows: Chinese experimental mini swine were given D-galactosamine to build models of acute liver failure. Thirty-four pigs were randomly divided into five groups. In the control group(A),the normal saline was injected into liver via portal veins after 24 h; in IL-1Ra group(B), IL-1Ra was injected via ear veins 6 h before normal saline; In the MSCs transplantation group (C), 8 * 107 MSCs were injected into liver via portal veins after 24 h; IL-1Ra together with MSCs transplantation group(D) and nanopaticles group(E) as follows: on the one hand, 8 * 107 MSCs were injected into liver via portal veins after 24 h, on the other hand, rhIL-1Ra in group C or IL-1Ra chitosan nanopaticles in group D was injected via ear veins respectively at 6 h before. Liver function, serum inflammation and pathological changes were measured. The fate of MSCs was also observed.</p><p><b>RESULTS</b>The profiles in vitro shown that there was a steady-state release after a fast linear release; The live targeting of the lactosylated chitosan-based nanoparticles was achieved by ligand-receptor specificity; The biochemical assay, the serum inflammation lever and pathological changes of the nanopaticles group were all greatly different from the other groups, the hepatocytes grow rate was significantly improved after 1 week; The liver engraftment was very low in group C and D with significantly higher numbers found in nanopaticles group, but the differentiation of MSCs after 2 weeks relatively rare; western blot showed that there was more HGF and VEGF secreted in nanopaticles group.</p><p><b>CONCLUSION</b>IL-lRa-loaded lactosylated chitosan-based nanopaticles have significant liver targeting abilities and slow release characteristics in PBS solution. The combined therapy showed great synergistic effects through suppression of liver inflammation and paracrine.</p>

New evidence of porcine endogenous retrovirus transmission with new bio-artificial liver system: a experimental study / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the potential transmissibility of porcine endogenous retrovirus (PERV) from a newly-developed porcine hepatocyte bioartificial liver (BAL) system prior to human clinical trial by using a live canine model.</p><p><b>METHODS</b>Five normal beagles were treated with the new BAL support system for six hours. Samples of plasma from the BAL system and whole blood from the beagles were collected at regular intervals over the six month study period. DNA and RNA were isolated from both the peripheral blood mononuclear cells (PBMCs) and plasma for evaluation by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR, respectively, to detect PERV and the Sus scrofa cytochrome B normalization standard. In addition, RT activity and the in vitro infectivity of the plasma were detected in HEK293 cells.</p><p><b>RESULTS</b>All five beagles remained in stable physical health throughout the treatment and survived until the end of the study. PERV RNA-positivity and RT activity were only detected in the plasma samples from the 3rd BAL treatment cycle. All other samples, including PBMCs and plasma, were negative for PERV RNA, PERV DNA, and RT activity. In addition, none of the sera samples showed in vitro infectivity.</p><p><b>CONCLUSION</b>Application of our BAL system does not lead to PERV transmission.</p>

The efficacy research of multi-layer flat-plate bioartificial liver on acute liver failure / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of newly developed multi-layer flat-plate bioartificial liver in treatment of canines with acute liver failure.</p><p><b>METHODS</b>Porcine hepatocytes and bone marrow mesenchymal stem cells were cocultured in newly developed multi-layer flat-plate bioreactor. Acute liver failure in canine models was induced by D-galactosamine administration.Sixteen canine models were divided into two groups: treatment group (n = 8) and control group (n = 8). Biochemical parameters were determined for 7 days after treatment and liver specimens were collected for histological analysis.</p><p><b>RESULTS</b>Hepatic encephalopathy and general conditions were significantly improved in the treatment group, but no changes in the control group. Alanine aminotransferase was significantly decreased from (1512 ± 183) U/L to (86 ± 25) U/L in the treatment group, aspartate aminotransferase was significantly decreased from (1472 ± 365) U/L to (46 ± 11) U/L, lactate dehydrogenase was significantly decreased from (463 ± 76) U/L to (312 ± 84) U/L, total bilirubin was significantly decreased from (28.8 ± 6.2) µmol/L to (12.5 ± 3.6) µmol/L, ammonia was significantly decreased from (56 ± 15) µmol/L to (34 ± 10) µmol/L, and prothrombin time were significantly decreased in the treatment group but increased in the control group, albumin was improved in the treatment group but decreased in the control group. There were 5 canines survived in the treatment group but only 3 in the control group. But there was no difference on survival rates between the two group (P = 0.294).</p><p><b>CONCLUSION</b>The application of newly developed multi-layer flat-plate bioartificial liver system was effective in the treatment of canines with acute liver failure.</p>