In:
Gut, BMJ, Vol. 70, No. 3 ( 2021-03), p. 567-574
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0017-5749
,
1468-3288
DOI:
10.1136/gutjnl-2019-319960
Language:
English
Publisher:
BMJ
Publication Date:
2021
detail.hit.zdb_id:
1492637-4
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