Liver-specific extracellular matrix hydrogel promotes liver-specific functions of hepatocytes in vitro and survival of transplanted hepatocytes in vivo

Hiroyuki Ijima, Shintaro Nakamura, Ronald Perocho Bual, Kozue Yoshida

Research output: Contribution to journalArticle

Abstract

A solubilized liver-specific extracellular matrix (L-ECM) substratum was obtained by decellularization of porcine liver using Triton X-100 and pepsin treatments. The L-ECM was able to immobilize hepatocyte growth factor at a high efficiency of 87%. L-ECM gelled spontaneously in a physiologically neutral environment. Primary hepatocytes embedded in the L-ECM gel showed a high albumin synthesis activity and ethoxyresorufin-O-deethylase (EROD) activity even at 3 weeks in culture. In addition, the L-ECM gel-embedded hepatocytes implanted subcutaneously into partial hepatectomized rats showed a high survival rate (18%) and formed a large liver tissue-like structure. Their efficiencies of EROD activity and large liver tissue-like structure formation were about twice those of collagen gel-embedded hepatocytes. Based on these results, we clarified the effectiveness of L-ECM gel as a substrate for hepatocyte culture and transplantation.

Original languageEnglish
JournalJournal of Bioscience and Bioengineering
DOIs
Publication statusPublished - Jan 1 2019

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Hydrogel
Hydrogels
Liver
Extracellular Matrix
Hepatocytes
Gels
Cytochrome P-450 CYP1A1
Tissue
In Vitro Techniques
Hepatocyte Growth Factor
Pepsin A
Octoxynol
Collagen
Rats
Albumins
Swine
Transplantation
Substrates

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

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title = "Liver-specific extracellular matrix hydrogel promotes liver-specific functions of hepatocytes in vitro and survival of transplanted hepatocytes in vivo",
abstract = "A solubilized liver-specific extracellular matrix (L-ECM) substratum was obtained by decellularization of porcine liver using Triton X-100 and pepsin treatments. The L-ECM was able to immobilize hepatocyte growth factor at a high efficiency of 87{\%}. L-ECM gelled spontaneously in a physiologically neutral environment. Primary hepatocytes embedded in the L-ECM gel showed a high albumin synthesis activity and ethoxyresorufin-O-deethylase (EROD) activity even at 3 weeks in culture. In addition, the L-ECM gel-embedded hepatocytes implanted subcutaneously into partial hepatectomized rats showed a high survival rate (18{\%}) and formed a large liver tissue-like structure. Their efficiencies of EROD activity and large liver tissue-like structure formation were about twice those of collagen gel-embedded hepatocytes. Based on these results, we clarified the effectiveness of L-ECM gel as a substrate for hepatocyte culture and transplantation.",
author = "Hiroyuki Ijima and Shintaro Nakamura and Bual, {Ronald Perocho} and Kozue Yoshida",
year = "2019",
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T1 - Liver-specific extracellular matrix hydrogel promotes liver-specific functions of hepatocytes in vitro and survival of transplanted hepatocytes in vivo

AU - Ijima, Hiroyuki

AU - Nakamura, Shintaro

AU - Bual, Ronald Perocho

AU - Yoshida, Kozue

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N2 - A solubilized liver-specific extracellular matrix (L-ECM) substratum was obtained by decellularization of porcine liver using Triton X-100 and pepsin treatments. The L-ECM was able to immobilize hepatocyte growth factor at a high efficiency of 87%. L-ECM gelled spontaneously in a physiologically neutral environment. Primary hepatocytes embedded in the L-ECM gel showed a high albumin synthesis activity and ethoxyresorufin-O-deethylase (EROD) activity even at 3 weeks in culture. In addition, the L-ECM gel-embedded hepatocytes implanted subcutaneously into partial hepatectomized rats showed a high survival rate (18%) and formed a large liver tissue-like structure. Their efficiencies of EROD activity and large liver tissue-like structure formation were about twice those of collagen gel-embedded hepatocytes. Based on these results, we clarified the effectiveness of L-ECM gel as a substrate for hepatocyte culture and transplantation.

AB - A solubilized liver-specific extracellular matrix (L-ECM) substratum was obtained by decellularization of porcine liver using Triton X-100 and pepsin treatments. The L-ECM was able to immobilize hepatocyte growth factor at a high efficiency of 87%. L-ECM gelled spontaneously in a physiologically neutral environment. Primary hepatocytes embedded in the L-ECM gel showed a high albumin synthesis activity and ethoxyresorufin-O-deethylase (EROD) activity even at 3 weeks in culture. In addition, the L-ECM gel-embedded hepatocytes implanted subcutaneously into partial hepatectomized rats showed a high survival rate (18%) and formed a large liver tissue-like structure. Their efficiencies of EROD activity and large liver tissue-like structure formation were about twice those of collagen gel-embedded hepatocytes. Based on these results, we clarified the effectiveness of L-ECM gel as a substrate for hepatocyte culture and transplantation.

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