Correlation of phospholipidosis between mouse liver three dimensional (3D) organoids and in vivo mouse

Abstract

The purpose of this study was to test whether the phenomena of phospholipidosis in mouse liver organoids was identical with that in in vivo mouse toxicity studies. For this purpose, the organoids were differentiated from liver stem cells of a C57BL/6 mouse and three compounds, amiodarone, tamoxifen and thioridazine, were treated to induce DIPL to the organoids for 72 hours. After differentiation, the organoids displayed compact spherical appearance composed of uniformly polygonal cells. Furthermore, the organoids showed a notable lower expression of adult stem cell genes, whereas hepatic progenitor/biliary gene and early hepatocyte gene levels were higher than those of the liver stem cells. The electron microscopy examination showed the intracytoplasmic aggregations of the multilamellar bodies, a hallmark of DIPL, in amiodarone-treated organoids. And histological examination and gene expression associated with DIPL supported the result from electron microscopy. Our findings suggest that mouse liver organoids can reflect well the expected or well-known outcomes in phospholipidosis-induced in vivo mouse and can support further researches for predicting the DIPL in liver organoids.