Intact extracellular matrix component promotes maintenance of liver-specific functions and larger aggregates formation of primary rat hepatocytes

Ronald P Bual; Hiroyuki Ijima

doi:10.1016/j.reth.2019.08.006

Intact extracellular matrix component promotes maintenance of liver-specific functions and larger aggregates formation of primary rat hepatocytes

Regen Ther. 2019 Sep 17:11:258-268. doi: 10.1016/j.reth.2019.08.006. eCollection 2019 Dec.

Authors

Ronald P Bual^{1

2}, Hiroyuki Ijima¹

Affiliations

¹ Department of Chemical Engineering, Faculty of Engineering, Graduate School, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395 Japan.
² Department of Chemical Engineering & Technology, College of Engineering, Mindanao State University-Iligan Institute of Technology, Andres Bonifacio Avenue, Tibanga, 9200 Iligan City, Philippines.

Abstract

The extracellular matrix (ECM) in a liver-specific extracellular matrix (L-ECM) scaffold facilitates hepatocyte viability and maintains hepatocyte functions in vitro. However, whether an intact composition of ECM is required for an efficient ECM-based substrate design remains to be clarified. In this study, two L-ECM hydrogels, namely L-ECM I and L-ECM II, were prepared by pepsin solubilization at 4 °C and 25 °C, respectively. The solubility at 4 °C was 50% whereas that at 25 °C was 95%, thus indicating well-preserved L-ECM. Analysis confirmed higher ECM protein components (especially collagen) in L-ECM II, along with denser fiber network and larger fiber diameter. L-ECM II gel exhibited high compression strength and suitable viscoelastic properties. Furthermore, hepatocytes in L-ECM II showed higher expression of liver-specific functions in 3D culture and wider spread while maintaining the cell-cell contacts in 2D culture. Therefore, an intact L-ECM is important to realize effective substrates for liver tissue engineering.

Keywords: Hepatocytes; Hydrogel; Liver-specific extracellular matrix; Scaffold; Tissue engineering.