サカグチ　カツヒサ   SAKAGUCHI Katsuhisa   坂口　勝久    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	In vitro ballooned hepatocytes can be produced by primary human hepatocytes and hepatic stellate cell sheets.
掲載誌名	正式名：Scientific reports 略　 称：Sci Rep ISSNコード：20452322/20452322
掲載区分	国外
巻・号・頁	12(1),pp.5341
著者・共著者	HASUI Nobuhiro†, SAKAGUCHI Katsuhisa*, OGAWA Tetsuya, SAKAMOTO Yoshihiro, SHIMIZU Tatsuya*
担当区分	2nd著者,責任著者
発行年月	2022/03/29
概要	Despite the increasing prevalence of Nonalcoholic steatohepatitis (NASH) worldwide, there is no effective treatment available for this disease. "Ballooned hepatocyte" is a characteristic finding in NASH and is correlated with disease prognosis, but their mechanisms of action are poorly understood; furthermore, neither animal nor in vitro models of NASH have been able to adequately represent ballooned hepatocytes. Herein, we engineered cell sheets to develop a new in vitro model of ballooned hepatocytes. Primary human hepatocytes (PHH) and Hepatic stellate cells (HSC) were co-cultured to produce cell sheets, which were cultured in glucose and lipid containing medium, following which histological and functional analyses were performed. Histological findings showed hepatocyte ballooning, accumulation of fat droplets, abnormal cytokeratin arrangement, and the presence of Mallory-Denk bodies and abnormal organelles. These findings are similar to those of ballooned hepatocytes in human NASH. Functional analysis showed elevated levels of TGFβ-1, SHH, and p62, but not TNF-α, IL-8. Exposure of PHH/HSC sheets to a glucolipotoxicity environment induces ballooned hepatocyte without inflammation. Moreover, fibrosis is an important mechanism underlying ballooned hepatocytes and could be the basis for the development of a new in vitro NASH model with ballooned hepatocytes.
DOI	10.1038/s41598-022-09428-x
PMID	35351975