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

Ijima, Hiroyuki, Nakamura, Shintaro, Bual, Ronald Perocho, Yoshida, Kozue
Journal of bioscience and bioengineering 2019
albumins, collagen, extracellular matrix, hepatocyte growth factor, hepatocytes, hydrogels, liver, octoxynol, pepsin, rats, solubilization, survival rate, swine
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.