Vascularized subcutaneous human liver tissue from engineered hepatocyte/fibroblast sheets in mice

Biological Engineering Society

Subcutaneous liver tissue engineering is an attractive and minimally invasive approach used to curative treat hepatic failure and inherited liver diseases. However, graft failure occurs frequently due to insufficient infiltration of blood vessels (neoangiogenesis), while the maintenance of hepatocyte phenotype and function requires in vivo development of the complex cellular organization of the hepatic lobule. Here we describe a subcutaneous human liver construction allowing for rapidly vascularized grafts by transplanting engineered cellular sheets consisting of human primary hepatocytes adhered onto a fibroblast layer. The engineered hepatocyte/fibroblast sheets (EHFSs) showed superior expression levels of vascularization-associated growth factors (vascular endothelial growth factor, transforming growth factor beta 1, and hepatocyte growth factor) in vitro. EHFSs developed into vascularized subcutaneous human liver tissues contained glycogen stores, synthesized coagulation factor IX, and showed significantly higher synthesis rates of liver-specific proteins (albumin and alpha 1 anti-trypsin) in vivo than tissues from hepatocyte-only sheets. The present study describes a new approach for vascularized human liver organogenesis under mouse skin. This approach could prove valuable for establishing novel cell therapies for liver diseases.;開始ページ : 66;終了ページ : 75;元資料の権利情報 : (C) 2015 Elsevier Ltd. All rights reserved.

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書名 Vascularized subcutaneous human liver tissue from engineered hepatocyte/fibroblast sheets in mice
著作者等 Biological Engineering Society
Elsevier Science Publishers
堺 裕輔
書名別名 肝細胞/線維芽細胞複合シートによる血管誘導皮下性ヒト肝組織の構築
出版元 Elsevier Ltd.
ページ数 v.
大きさ 30 cm
ISSN 01429612
NCID AA11522637
AA00110092
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言語 英語
出版国 イギリス
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