Hepatectomised patient sera promote hepatocyte differentiation of human-induced pluripotent stem cells

BackgroundHuman induced pluripotent stem cells, which can be differentiated into hepatocyte-like cells, could provide a source for liver regeneration and bio-artificial liver devices. However, the functionality of hepatocyte-like cells is significantly lower than that of primary hepatocytes.AimsTo investigate whether serum from patients undergoing hepatectomy might promote differentiation from human induced pluripotent stem cells to hepatocyte-like cells.MethodsSerum from patients undergoing hepatectomy (acquired pre-hepatectomy and 3 hours, 1 day and 3 days post-hepatectomy) was used to replace foetal bovine serum when differentiating human induced pluripotent stem cells into hepatocyte-like cells. Properties of hepatocyte-like cells were assessed and compared with cells cultured in foetal bovine serum.ResultsThe differentiation efficiency and functionality of hepatocyte-like cells cultured in human serum 3 hours and 1 day post-hepatectomy were superior to those cultured in foetal bovine serum and human serum pre-hepatectomy. Human serum 3 days post-hepatectomy had an equal effect to that of human serum pre-hepatectomy. Some cytochrome P450 isozyme transcript levels of hepatocyte-like cells cultured in human serum were higher than those cultured in foetal bovine serum.ConclusionHuman serum, particularly that acquired relatively soon after hepatectomy, can enhance the differentiation efficiency and functionality of hepatocyte-like cells derived from human induced pluripotent stem cells.