3D human liver organoids: An in vitro platform to investigate HBV infection, replication and liver tumorigenesis

2021 ◽  
Vol 506 ◽  
pp. 35-44
Author(s):  
Shringar Rao ◽  
Tanvir Hossain ◽  
Tokameh Mahmoudi
2019 ◽  
Vol 70 (1) ◽  
pp. e708
Author(s):  
Chuan Kok Lim ◽  
Bang M Tran ◽  
Byron Shue ◽  
Nicholas Eyre ◽  
Dustin Flanagan ◽  
...  

2020 ◽  
Vol 12 (8) ◽  
pp. 607-617
Author(s):  
Lulu Sun ◽  
Lijian Hui

Abstract Understanding the development, regeneration, and disorders of the liver is the major goal in liver biology. Current mechanistic knowledge of human livers has been largely derived from mouse models and cell lines, which fall short in recapitulating the features of human liver cells or the structures and functions of human livers. Organoids as an in vitro system hold the promise to generate organ-like tissues in a dish. Recent advances in human liver organoids also facilitate the understanding of the biology and diseases in this complex organ. Here we review the progress in human liver organoids, mainly focusing on the methods to generate liver organoids, their applications, and possible future directions.


2019 ◽  
Author(s):  
Elisa De Crignis ◽  
Shahla Romal ◽  
Fabrizia Carofiglio ◽  
Panagiotis Moulos ◽  
Monique M.A. Verstegen ◽  
...  

AbstractThe molecular events that drive Hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose the use of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. We first describe a primary ex vivo HBV-infection model derived from healthy donor liver organoids after challenge with recombinant virus or HBV-infected patient serum. HBV infected organoids produced cccDNA, expressed intracellular HBV RNA and proteins, and produced infectious HBV. This ex vivo HBV infected primary differentiated hepatocyte organoid platform was amenable to drug screening for both anti-HBV activity as well as for drug-induced toxicity. We also studied HBV replication in transgenically modified organoids; liver organoids exogenously overexpressing the HBV receptor NTCP by lentiviral transduction were not more susceptible to HBV, suggesting the necessity for additional host factors for efficient infection. We also generated transgenic organoids harboring integrated HBV, representing a long-term culture system also suitable for viral production and the study of HBV transcription. Finally, we generated HBV-infected patient-derived liver organoids from non-tumor cirrhotic tissue of explants from liver transplant patients. Interestingly, transcriptomic analysis of patient-derived liver organoids indicated the presence of an aberrant early cancer gene signature, which clustered with the HCC cohort on the TCGA LIHC dataset and away from healthy liver tissue, and may provide invaluable novel biomarkers for disease surveillance and development of HCC in HBV infected patients.


HPB ◽  
2021 ◽  
Vol 23 ◽  
pp. S99-S100
Author(s):  
A. Gulla ◽  
J. Denkovskij ◽  
J. Novikova ◽  
A. Misiunas ◽  
D. Vitkus ◽  
...  
Keyword(s):  
3D Model ◽  

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elisa De Crignis ◽  
Tanvir Hossain ◽  
Shahla Romal ◽  
Fabrizia Carofiglio ◽  
Panagiotis Moulos ◽  
...  

The molecular events that drive Hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose the use of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. We first describe a primary ex vivo HBV-infection model derived from healthy donor liver organoids after challenge with recombinant virus or HBV-infected patient serum. HBV infected organoids produced cccDNA, HBeAg, expressed intracellular HBV RNA and proteins, and produced infectious HBV. This ex vivo HBV infected primary differentiated hepatocyte organoid platform was amenable to drug screening for both anti-HBV activity as well as for drug-induced toxicity. We also studied HBV replication in transgenically modified organoids; liver organoids exogenously overexpressing the HBV receptor NTCP after lentiviral transduction were not more susceptible to HBV, suggesting the necessity for additional host factors for efficient infection. We also generated transgenic organoids harboring integrated HBV, representing a long-term culture system also suitable for viral production and the study of HBV transcription. Finally, we generated HBV-infected patient-derived liver organoids from non-tumor cirrhotic tissue of explants from liver transplant patients. Interestingly, transcriptomic analysis of patient-derived liver organoids indicated the presence of an aberrant early cancer gene signature, which clustered with the HCC cohort on the TCGA LIHC dataset and away from healthy liver tissue, and may provide invaluable novel biomarkers for the development of HCC and surveillance in HBV infected patients.


2011 ◽  
Vol 49 (01) ◽  
Author(s):  
SA Hoffmann ◽  
M Lübberstedt ◽  
U Müller-Vieira ◽  
D Knobeloch ◽  
A Nüssler ◽  
...  

2020 ◽  
Author(s):  
H Gaitantzi ◽  
C Cai ◽  
S Asawa ◽  
K Böttcher ◽  
M Ebert ◽  
...  

2008 ◽  
Author(s):  
Cheng J. Cao ◽  
Gunda Reddy ◽  
Desmond I. Bannon ◽  
Mark S. Johnson

Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.


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