Integration of Endothelial Cell-Covered Hepatocyte Spheroids for Construction of Vascularized Liver Tissue

摘要

Tissue vascularization by coculture with endothelial cells has been studied for the creation of viable, large tissues for therapeutic use. To supply a sufficient mass of hepatocytes for cell transplantation, a high cell density tissue-like structure (organoid) is necessary because of the limited space for transplantation in the body. A spheroid is a spherical organoid assembled in vitro from monodispersed cells. Hepatocyte spheroids have a cell density close to that of native liver tissue and expressliver specific functions at a high level. Using novel culture techniques to produce different shapes of hepatocyte organoids, we previously demonstrated that hepatocyte organoids should be approximately 100 mu m in diameter to survive. Based on this evidence, the arrangement of endothelial cells within the hepatocyte organoid at regular 100 mu m intervals is a promising approach for the construction of a larger, vascularized liver tissue. The endothelial cell-covered hepatocyte spheroid is a candidatetissue unit to produce the alignment of endothelial cells at regular intervals in large hepatic tissues to allow for the in vitro construction of a vascularized tissue.