RT Journal Article
SR Electronic
T1 Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP gutjnl-2019-319960
DO 10.1136/gutjnl-2019-319960
A1 Huayu Yang
A1 Lejia Sun
A1 Yuan Pang
A1 Dandan Hu
A1 Haifeng Xu
A1 Shuangshuang Mao
A1 Wenbo Peng
A1 Yanan Wang
A1 Yiyao Xu
A1 Yong-Chang Zheng
A1 Shunda Du
A1 Haitao Zhao
A1 Tianyi Chi
A1 Xin Lu
A1 Xinting Sang
A1 Shouxian Zhong
A1 Xin Wang
A1 Hongbing Zhang
A1 Pengyu Huang
A1 Wei Sun
A1 Yilei Mao
YR 2020
UL http://gut.bmj.com/content/early/2020/05/20/gutjnl-2019-319960.abstract
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.