Decellularized liver matrix as substrates for rescue of acute hepatocytes toxicity

J Biomed Mater Res B Appl Biomater. 2020 May;108(4):1592-1602. doi: 10.1002/jbm.b.34506. Epub 2019 Oct 23.

Abstract

More and more scholars regard the lesion of liver cirrhosis as a series of progressive clinical stages. Besides, liver cirrhosis is a late stage of scarring (fibrosis) of the liver, and has long been a common cause of death for the global adult population, thus, the treatment of liver cirrhosis is a key point investigated in the biomedical field. Here, we propose a novel hypothesis; if decellularized liver matrix (DLM) is possible injected into the injurant-induced fiberized liver via the hepatic portal vein to thoroughly repair the liver, it may be an effective therapeutic method for liver fibrosis or even liver cirrhosis. This study mixed rat DLM with gelatin-hydroxyphenylpropionic acid (Glt-HPA) to form a three-dimensional structure to simulate the in vivo liver environment, and cultured the primary rat hepatocytes in it. Afterward, the hepatocytes were treated using D-galactosamine (GaIN), CHCl3 , and CCl4 -containing medium to simulate the toxin-mediated liver fibrosis in vitro. Finally, they were cultured in a DLM-containing medium to observe the viability and functions of the damaged hepatocytes, and the hypothesis of this research was proved, meaning that Glt-HPA-DLM acting on damaged hepatocytes may repair them. Results have shown that Glt-HPA-DLM was effective for hepatocytes culture and repaired injured hepatocytes from GaIN, CHCl3 , and CCl4 (albumin synthesis was increased by 219, 108, and 12%, respectively, whereas relative lactate dehydrogenase activity was reduced by 38, 68, and 67%, after 5 days of culture, separately). This research shows promising effects against hepatic fibrosis and may have potential for liver cirrhosis in vivo.

Keywords: CHCl3 and CCl4-induced liver injury; D-galactosamine; decellularized liver matrix; gelatin-hydroxyphenylpropionic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Extracellular Matrix / chemistry*
  • Hepatocytes / metabolism*
  • Liver / chemistry*
  • Liver / metabolism
  • Liver Cirrhosis* / metabolism
  • Liver Cirrhosis* / pathology
  • Liver Cirrhosis* / therapy
  • Male
  • Rats
  • Rats, Sprague-Dawley