Hepatocytic differentiation of iPS cells on decellularized liver tissue

Abstract

Decellularized tissues (DETs) have been attracting great attention as scaffolds for tissue-engineering approaches. Recently, some studies have reported that decellularized liver tissues (DLT) can provide an excellent environment for the hepatocytic differentiation of hepatic stem/progenitor cells that were already committed to the hepatocyte lineage. However, the effects of DLT on the hepatocytic differentiation of induced pluripotent stem cells (iPSs) have not yet been established. Here we studied the hepatocytic differentiation of iPSs on DLT and decellularized heart tissues (DHT) in order to determine the tissue-specific effects of DETs on iPSs differentiation. Our results showed that DLTs led to higher gene expression levels of forkhead box A2 (a marker of endoderm) and CCAAT/enhancer binding protein-α (master transcription factor to hepatocyte differentiation), alpha-fetoprotein (a marker of fetal hepatocyte,), and albumin (a marker of fetal andmaturehepatocyte) of iPSs than on DHTs. Furthermore, gene expression levels of tyrosine aminotransferase (a marker of mature hepatocyte) were higher on DLT than that on DHT, and immunocytochemical analysis and ELISA assay showed that albumin secretion level of iPSs on DLT was higher than that on DHT. Our study demonstrated that the use of DLTs led to mature hepatocytic differentiation levels of iPSs compared to DHTs, which provides a better niche for iPSs cell engineering and enables the preparation of useful mature cells for regenerative therapy.