Tissue array substratum composed of histological sections: a new platform for orienting differentiation of embryonic stem cells towards hepatic lineage.

Culture technologies for differentiating embryonic stem cells (ESCs) into hepatic cells generally require some growth factors for several days. Here we present a new technology for efficiently differentiating mouse ESCs into hepatocyte-like cells in a supplement-free basal medium by using a tissue array substratum composed of histological sections. The substratum was prepared from liver tissues in various stages after administration of carbon tetrachloride to mice. The substrata derived from regenerating livers enhanced cell attachment, supported growth as clusters, and induced differentiation into cells expressing albumin, although the substrata from injured livers did not. In particular, the cells cultured on the most-proliferative regenerating liver-derived section substratum reconstructed the hepatic cord-like structures with bile canaliculus-like aspects in which some binucleated cells were involved, secreted albumin, and expressed cytochrome P450IA1 activity within a few days. This culture technology also provides a novel concept for Histomics, categorizing the features of different tissues based on the behavior of a cell line cultured on their array substratum (i.e., tissuome).