PT  - JOURNAL ARTICLE
AU  - Huayu Yang
AU  - Lejia Sun
AU  - Yuan Pang
AU  - Dandan Hu
AU  - Haifeng Xu
AU  - Shuangshuang Mao
AU  - Wenbo Peng
AU  - Yanan Wang
AU  - Yiyao Xu
AU  - Yong-Chang Zheng
AU  - Shunda Du
AU  - Haitao Zhao
AU  - Tianyi Chi
AU  - Xin Lu
AU  - Xinting Sang
AU  - Shouxian Zhong
AU  - Xin Wang
AU  - Hongbing Zhang
AU  - Pengyu Huang
AU  - Wei Sun
AU  - Yilei Mao
TI  - Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure
AID  - 10.1136/gutjnl-2019-319960
DP  - 2020 May 20
TA  - Gut
PG  - gutjnl-2019-319960
4099  - http://gut.bmj.com/content/early/2020/05/20/gutjnl-2019-319960.short
4100  - http://gut.bmj.com/content/early/2020/05/20/gutjnl-2019-319960.full
AB  - Objective Shortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo.Design 3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production.Results 3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah-/-Rag2-/- mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice.Conclusions Our results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.