Hybrid organoids consisting of extracellular matrix gel particles and hepatocytes for transplantation

Abstract

Hepatocyte transplantation is a potential therapy for treating various liver diseases. However, oxygen shortage leading to loss of hepatocyte function becomes a limitation following hepatocyte transplantation. To overcome this problem, we developed a hybrid organoid, consisting of growth factor (GF)-immobilizable gel particles combined with hepatocytes. Benefits of the hybrid organoid were evaluated in three groups: (i) hybrid organoid consisting of cells and GF-immobilizable gel particles (HG-C); (ii) hybrid organoid consisting of cells and gel particles (G-C); and (iii) cells suspended in collagen (C-C). We found liver-specific functions of HG-C were maintained longer than in the other conditions during in vitro culture. Furthermore, after transplantation, HG-C was effective in maintaining viability of transplanted hepatocytes and promoting angiogenesis around the hepatocytes. In summary, transplantation of HG-C is a potential method for future liver tissue engineering.

Keywords: Animal cell culture; Growth factor; Hepatocyte transplantation; Immobilization; Organoid; Tissue engineering.