アクティブボード・2011年 1月
・・・・・2011年 1月 3日更新・・・・・
研究発表を行った学会;
・第33回日本分子生物学会年会
2010年12月7日〜10日(神戸)
タイトル;Efficient differentiation of mouse and human ES/iPS cells into hepatic cells using feeder free basement membrane substratum.
発表者; 白木 伸明 氏
(熊本大学 発生医学研究所 多能性幹細胞分野)
Abstract;
Liver is an essential organ that assumes the responsibility for many kinds of sophisticated metabolism. Biotransformation of xenobiotics usually results in detoxification but sometime happens to induce their bioactivation; the produced metabolites acquire stronger toxicity than their parent drug molecule. Although primary culture of hepatocytes is a powerful tool to trace the bioactivation of xenobiotics, the cells are inclined to reduce that important performance in culture. In addition, the bioactivation considerably varies depending upon characteristics of donors. ES cells are pluripotent cells derived from the inner cell mass of the blastocyst. Lines of evidence have shown that in many cases ES cells seem to recapitulate normal developmental processes, thereby suggest that ES cells provide an attractive source for an innovative strategy of drug-screening. Moreover, induced pluripotent stem (iPS) cells established from somatic cells further also are also expected as a surrogate cell source for regenerative medicine. Previously, we report that modification of the culture condition by culturing ES cells on a supportive cell line, M15 cells, promises a selective induction of hepatic differentiation at a high efficiency. However, an alternative culture model, that is, without a feeder is also valuable for molecular analysis of hepatic differentiation. Previously we reported the basement membrane formation by culturing epithelial cells in vitro and the terminal differentiation of tracheal basal cells to ciliated ones on a novel substratum of synthesized basement membrane (sBM). Here we report that a feeder-free procedure using sBM substratum, instead of M15 cells, enabled the hepatic differentiation of both mouse and human ES/iPS cells. In the optimal cultures some growth factors significantly promoted hepatic maturation. In conclusion, the feeder-free procedure for hepatic differentiation is so useful for the elucidation of molecular mechanism concerning hepatic fate decision and enables an attractive approach for pharmaceutical developments and pharmacological researches as the alternative culture model.