Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure

doi:10.1136/gutjnl-2019-319960

	Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure
	Yang, Huayu 1; Sun, Lejia 1; Pang, Yuan 2,3,4; Hu, Dandan 1,5; Xu, Haifeng 1; Mao, Shuangshuang 2,3,4; Peng, Wenbo6 ; Wang, Yanan 7,8; Xu, Yiyao 1; Zheng, Yong-Chang 1; Du, Shunda 1; Zhao, Haitao 1; Chi, Tianyi 1; Lu, Xin 1; Sang, Xinting 1; Zhong, Shouxian 1; Wang, Xin 9,10,11; Zhang, Hongbing 7,8; Huang, Pengyu6,12 ; Sun, Wei 2,3,4,13; Mao, Yilei 1
	2021-03
发表期刊	GUT
ISSN	0017-5749
EISSN	1468-3288
卷号	70 期号:3 页码:567-574
DOI	10.1136/gutjnl-2019-319960
摘要	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.
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收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Gastroenterology & Hepatology
WOS类目	Gastroenterology & Hepatology
WOS记录号	WOS:000616739300017
出版者	BMJ PUBLISHING GROUP
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125759
专题	生命科学与技术学院_博士生生命科学与技术学院_PI研究组_黄鹏羽组
通讯作者	Huang, Pengyu; Sun, Wei; Mao, Yilei
作者单位	1.PUMC & Chinese Acad Med Sci, Peking Union Med Coll PUMC Hosp, Dept Liver Surg, Beijing, Peoples R China; 2.Tsinghua Univ, Biomfg Ctr, Dept Mech Engn, Beijing, Peoples R China; 3.Tsinghua Univ, Biomfg & Rapid Forming Technol Key Lab Beijing, Beijing, Peoples R China; 4.Tsinghua Univ, Overseas Expertise Intro Ctr Discipline Innovat, Beijing, Peoples R China; 5.Sun Yat Sen Univ Canc Ctr, Dept Hepatobiliary Surg, Guangzhou, Guangdong, Peoples R China; 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 7.Inst Basic Med Sci Chinese Acad Med Sci, Dept Physiol, State Key Lab Med Mol Biol, Beijing, Peoples R China; 8.Peking Union Med Coll, Sch Basic Med, Beijing, Peoples R China; 9.Inner Mongolia Univ, Res Ctr Lab Anim Sci, Hohhot, Inner Mongolia, Peoples R China; 10.Cell Lab Tech Inc, Hepatosci Sect, Sunnyvale, CA USA; 11.Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA; 12.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China; 13.Drexel Univ, Dept Mech Engn, Philadelphia, PA 19104 USA
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yang, Huayu,Sun, Lejia,Pang, Yuan,et al. Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure[J]. GUT,2021,70(3):567-574.
APA	Yang, Huayu.,Sun, Lejia.,Pang, Yuan.,Hu, Dandan.,Xu, Haifeng.,...&Mao, Yilei.(2021).Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure.GUT,70(3),567-574.
MLA	Yang, Huayu,et al."Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure".GUT 70.3(2021):567-574.