Hepatocyte growth on polycapronolactone and 2-hydroxyethylmethacrylate nanofiber sheets enhanced by bone marrow-derived mesenchymal stromal cells.

BACKGROUND/AIMS: The development of hepatocyte-based Bioartificial Liver Assist Devices, intended for the therapy of chronic and fulminant liver failure, is one of the important tasks in the area of tissue engineering. New advances in the development of semipermeable non-woven nanofiber biomaterials and the co-cultivation of bone marrow mesenchymal stromal cells (BMSC) and hepatocytes could be utilized in order to maintain hepatocyte cultures in these devices. METHODOLOGY: We have compared rat hepatocyte growth on nanofiber biomaterials from different polymers, 2-hydroxyethylmethacrylate (HEMA) and ethoxyethylmethacrylate (EOEMA) copolymers, polyurethane (PUR), chitosan and polycapronolactone (PCL) spun from different solvent mixtures. RESULTS: In all cases the adhesion of hepatocytes to nanofibers was significantly better/stronger than to unstructured polymer surfaces; coating the nanofibers with collagen did not increase cell adhesion. We found the best hepatocyte adhesion on HEMA/EOEMA copolymer nanofibers and PCL nanofibers spun from a mixture of ethylacetate and dimethyl sulphoxide. Using a migration assay, we observed the migration of BMSC towards hepatocytes; hepatocytes cocultivated with BMSC excreted lower amounts of stress enzymes. CONCLUSIONS: The results demonstrate that nonwoven nanofiber layers, particularly those containing BMSC, are a suitable biocompatible support for functional hepatocyte cultures and that they can be used in a laboratory bioreactor or potentially in clinical setting.

Cerebral microdialysis reflects the neuroprotective effect of fractionated plasma separation and adsorption in acute liver failure better and earlier than intracranial pressure: a controlled study in pigs.

BACKGROUND: Cerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF). The effectiveness of treatments that address intracranial hypertension is generally assessed by measuring intracranial pressure (ICP). The aim of this study was to determine the role of cerebral microdialysis in monitoring the efficacy of fractionated plasma separation and adsorption (FPSA) treatment for ALF. We hypothesized that in ALF cerebral microdialysis reflects the benefits of FPSA treatment on cerebral edema before ICP. METHODS: A surgical resection model of ALF was used in 21 pigs. We measured plasma ammonia concentration, brain concentrations of glucose, lactate, pyruvate, glutamate and glutamine, and ICP. Animals were randomized into three groups: in one group eight animals received 6 hours of FPSA treatment 2 hours after induction of ALF; in another group 10 animals received supportive treatment for ALF only; and in the final group three underwent sham surgery. RESULTS: The ICP was significantly higher in the ALF group than in the FPSA group 9 hours after surgery. The lactate/pyruvate (L/P) ratio was significantly lower in the FPSA group than the ALF group 5 hours after surgery, before any significant difference in ICP was detected. Indeed, significant changes in the L/P ratio could be observed within 1 hour of treatment. Glutamine levels were significantly lower in the FPSA group than the ALF group between 6 hours and 10 hours after surgery. CONCLUSIONS: Brain lactate/pyruvate ratio and concentration of glutamine measured by cerebral microdialysis reflected the beneficial effects of FPSA treatment on cerebral metabolism more precisely and rapidly than ICP in pigs with fulminant ALF. The role of glutamine as a marker of the efficacy of FPSA treatment for ALF appears promising, but needs further evaluation.

S-adenosylmethionine does not reduce ischaemia-reperfusion injury to a marginal liver graft in an in vivo experiment.

BACKGROUND/AIMS: There are a limited number of appropriate cadaver liver donors. One possible solution is the use of marginal liver grafts from cadaver donors for liver transplantation. METHODOLOGY: Rats with liver steatosis were divided into four containing seven animals each: I-a: steatotic liver grafts; +S-adenosylmethionine; I-b: steatotic liver grafts were transplanted; no S-adenosylmethionine; II-a: normal liver grafts, +S-adenosylmethionine; II-b: normal liver grafts. Blood samples were taken at days -1, 3 and 14. RESULTS: ALT values at day 14: 1.75 ± 1.10µkat/L (in group I-a), 1.91 ± 1.41µkat/L (in group I-b), 2.13±1.85µkat/L (in group II-a) and 2.08 ± 1.35µkat/L (in group II-b). There were no significant differences between these values. GSH values at day 14 post-transplantation were: 44.90 ± 8.61µM/mg (in group I-a), 43.82±8.58µM/mg (in group I-b), 41.65 ± 4.87µM/mg (in group II-a) and 42.71 ± 4.17µM/mg (in control group II-b). CONCLUSIONS: Our study did not demonstrate the positive effect of S-adenosylmethionine on ischaemia-reperfusion injury during liver transplantation in rats.