IQB Handbook

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25ACHIEVEMENTPUBLICATIONKoui Y, Kido T, Ito T, Oyama H, Chen S-W and Miyajima A. An in vitro human liver model by iPSC-derived parenchymal and non-parenchymal cells. Stem Cell Rep. 9, 490-498, 2017. DOI:10.1016/j.stemcr.2017.06.010 Kamimoto K, Nakano Y, Miyajima A, and Itoh T. Multidimensional imaging of liver injury repair in mice reveals fundamental role of the ductular reaction. Communications Biology (2020) 3: 289. DOI:10.1038/s42003-020-1006-1Chen S-W, Himeno M, Koui Y, Sugiyama M, Nishitsuji H, Mizokami M, Shimotohno K, Miyajima A and Kido T. Modulation of Hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells. Sci. Rep. (2020) 10: 14349. DOI:10.1038/s41598-020-71453-5Directed differentiation of human induced pluripotent stem cells (hiPSCs) to liver progenitor cells (LPCs) and hepatocytes, as well as to liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), has been established. Co-culture of those iPSC-derived liver component cells enables us to construct functional human liver tissue ex vivo.MIYAJIMAATSUSHIPH.D. (1980) THE UNIVERSITY OF TOKYORESEARCH ASSISTANT (1980) SHIZUOKA UNIVERSITYCHIEF RESEARCHER (1988) DNAX RESEARCH INSTITUTE OF MOLECULAR & CELLULAR BIOLOGYPROFESSOR (1994)INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, THE UNIVERSITY OF TOKYODIRECTOR (2003-2009)INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, THE UNIVERSITY OF TOKYOPROJECT PROFESSOR (2018)IQB / INSTITUTE FOR QUANTITATIVE BIOSCIENCES, THE UNIVERSITY OF TOKYO●MEMBER■ PROJECT PROFESSOR :MIYAJIMA ATSUSHI■ PROJECT ASSOCIATE PROFESSOR :ITOH TOHRU■ PROJECT LECTURERE : KIDO TAKETOMO■ PROJECT RESEARCHER : TANAKA HIROKO■ PROJECT ACADEMIC SUPPORT SPECIALIST : KAMIYA YOSHIKO■ PROJECT ACADEMIC SUPPORT SPECIALIST : KOGA CHIZUKO■ PROJECT ACADEMIC SUPPORT SPECIALIST : HOSHINO YUKARI■ JSPS RESEARCH FELLOW : HIMENO MISAOPUBLICATIONPUBLICATIONevelopment of systems to prepare functional cells and tissues of sufficient quality and quantity is central to realization of stem cell-based therapy, drug screening and regenerative medicine. The liver is a central organ for metabolism and detoxification in the body and hence is one of the major targets for those applications. For the last two decades, our lab has been studying the molecular and cellular mechanisms underly-ing development of the liver, taking advantage of our originally developed methods to isolate and culture each type of liver component cells. During the course of liver organogene-sis, parenchymal hepatocytes develop from fetal liver progenitor cells, also known as hepatoblasts, through multiple modes of cell–cell interactions with other types of non-parenchymal cell populations including endothelial cells and mesenchymal cells. Based on our accumulated knowledge and expertise on the mechanistic basis of the liver development, we have successfully estab-lished culture systems to achieve directed differentiation of functional hepatocytes, as well as other non-parenchymal cells, from human induced pluripotent stem cells (iPSCs) through corresponding progenitor cell populations. Further application of three-di-mensional co-culture system have rendered those iPSC-derived liver cells to cooperatively organize functional liver tissues with remark-able metabolic activities. Similarly, we have also developed a culture system to generate pancreatic islet-like tissue structures contain-ing insulin-producing beta cells from human iPSCs. We are currently applying those iPSC-derived cells and tissues for regenera-tive medicine, drug discovery and disease modeling.D