Bioartificial liver system based on choanoid fluidized bed bioreactor improve the survival time of fulminant hepatic failure pigs

Abstract

Bioartificial liver (BAL) support system has been proposed as potential treatment method for end-stage liver diseases. We described an improved BAL system based on a choanoid fluidized bed bioreactor containing alginate-chitosan encapsulated primary porcine hepatocytes. The feasibility, safety, and efficiency of this device were estimated using an allogeneic fulminant hepatic failure (FHF) model. FHF was induced with intravenous administration of D-galactosamine. Thirty FHF pigs were divided into three groups: (1) an FHF group which was only given intensive care; (2) a sham BAL group which was treated with the BAL system with empty encapsulation, and (3) a BAL group which was treated with the BAL system containing encapsulated freshly isolated primary porcine hepatocytes. The survival times and biochemical parameters of these animals were measured, and properties of the encapsulations and hepatocytes before and after perfusion were also evaluated. Compared to the two control groups, the BAL-treated group had prolonged the survival time and decreased the blood lactate levels, blood glucose, and amino acids remained stable. No obvious ruptured beads or statistical decline in viability or function of encapsulated hepatocytes were observed. This new fluidized bed BAL system is safe and efficient. It may represent a feasible alternative in the treatment of liver failure.

Efficacy of coupled low-volume plasma exchange with plasma filtration adsorption in treating pigs with acute liver failure: A randomised study

“…The former includes hepatic ischemia and hepatectomy, and the latter are based on administering drugs and toxins, such as acetaminophen, D-galactosamine, azoxymethane, concanavalin A, and thioacetamide [37,38]. Our study adopted a widely accepted ALF porcine model induced by D-galactosamine [39,40] because this model demonstrates high reproducibility and potential reversibility [30][31][32]41]. Notably, this pig model was highly similar to both clinical and laboratory indices of patients with drug-induced ALF and provided a suitable model to evaluate the efficacy of our novel Li-ALS treatment.…”

“…ALF was induced with D-galactosamine, as described previously by our laboratory [29][30][31][32]. Animals were fasted for 8 hours prior to catheterisation.…”

Development of a bioreactor based on magnetically stabilized fluidized bed for bioartificial liver

“…According to Lv G et al, the flow rate in their choanoid fluidized bed bioreactor was maintained about 25-35 mL/ min [15]. Under the same cross section (mean diameter: 50 mm), the flow rate in our MSFB system was estimated to reach 300 mL/min.…”

“…In general, most of the microcapsule-based bioreactors are designed on fixed bed or fluidized bed configuration [10,15,16]. The fixed bed reactors are superior in achieving maximization of hepatocytes density and minimization of dead volume [17].…”

Current Translational Challenges for Tissue Engineering: 3D Culture, Nanotechnology, and Decellularized Matrices

“…Bioartificial liver support systems based on fluidized beds have also shown promise for potential clinical application. Primary porcine hepatocytes encapsulated within alginate-chitosan beads filtered circulating plasma of liver failure model porcine patients, maintaining essential liver functions and significantly extending survival as compared to untreated animals [89]. However, the use of a bioreactor system beyond preconditioning for implantation or alleviation of disease symptoms does not provide a truly lasting solution to the clinical needs of the patient.…”