The Influence of Membrane Molecular Weight Cutoff on a Novel Bioartificial Liver

Abstract

Given the xenogeneic immune reaction relevant to the molecular weight cutoff of the membrane of a bioartificial liver (BAL) system, we investigated the influence of membrane molecular weight cutoff in our BAL system in this study. Acute liver failure in beagles was induced by d-galactosamine administration. Eight beagles were divided into two groups by the membrane molecular weight cutoff of the plasma component separator. Group 1 beagles were treated with BAL containing 200 kDa retention rating membrane. Group 2 beagles were treated with BAL containing 1200 kDa retention rating membrane. Each group underwent two 6-h BAL treatments that were performed on day 1 and day 21. The hemodynamic and hematologic response, humoral immune responses, and cytotoxic immune response to BAL therapy were studied before and after treatments. All beagles remained hemodynamically and hematologically stable during BAL treatments. BAL treatment was associated with a significant decline in levels of complement; however, a longer time of level maintenance was observed in Group 2. Group 2 beagles experienced a significant increase in levels of IgG and IgM after two BAL treatments. Significant levels of canine proteins were detected in BAL medium from Group 2; only trace levels of canine proteins were detected in BAL medium from Group 1. The posttreatment viability of co-culture cells in Group 2 was lower compared with Group 1, and the viability of co-culture cells after treatments was associated with deposition of canine proteins on the cells. Xenogeneic immune response was influenced by membrane molecular weight cutoff in the BAL.

A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes

“…Additionally, the cytotoxicity was reduced by heating the host serum for 30 min at 56°C, conditions known to denature the complement. Xhi et al and Zhang et al also reported similar results using a 200-kilodalton pore membrane and a 1200-kilodalton pore membrane [30,31]. Their results suggested that antibody-mediated immune responses involving complement systems occurred in a BAL system with a larger pore size.…”

Artificial Organs 2012: A Year in Review

“…Yue Zhang et al. of Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China studied the influence of membrane molecular weight cutoff in their bioartificial liver (BAL) using the acute liver failure model in beagles of d‐galactosamine administration. The Group 1 four beagles were treated with BAL containing 200 kDa retention plasma component membrane.…”

C3A Cells-Inoculated Affinity Membrane for Bilirubin Removal

“…Compared with traditional nonbiological artificial livers, BALs not only have a liver-specific detoxification function, but can also participate in the metabolism of three substances (sugar, protein, and fat) and secrete substances that promote the growth of liver cells, which can effectively replace the detoxification function and synthesis function of the liver. Although the existing bioartificial liver reactor system to some extent realizes the detoxification and biosynthesis functions of the liver, it is difficult to detoxify a large number of metabolites and toxic substances accumulated in the body of patients with liver failure by cultured liver cells, which may also have adverse effects on the survival and biological functions of the cells [8][9][10][11][12]. Therefore, the development of an efficient bioreactor that can effectively detoxify and maintain cell activity would significantly improve the efficiency of blood detoxification.…”

“…synthesis function of the liver. Although the existing bioartificial liver reactor system to some extent realizes the detoxification and biosynthesis functions of the liver, it is difficult to detoxify a large number of metabolites and toxic substances accumulated in the body of patients with liver failure by cultured liver cells, which may also have adverse effects on the survival and biological functions of the cells [8][9][10][11][12]. Therefore, the development of an efficient bioreactor that can effectively detoxify and maintain cell activity would significantly improve the efficiency of blood detoxification.…”