scholarly journals Progress in human liver organoids

2020 ◽  
Vol 12 (8) ◽  
pp. 607-617
Author(s):  
Lulu Sun ◽  
Lijian Hui
Keyword(s):  
Mouse Models ◽  
Human Liver ◽  
Major Goal ◽  
Future Directions ◽  
In Vitro System ◽  
Human Liver Cells ◽  
Human Livers ◽  
Liver Organoids ◽  
Complex Organ

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.

AAnti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Cells ◽  
Normal Weight ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Tnf Α ◽  
Anti Inflammatory

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.

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
Keyword(s):  
Human Liver ◽  
Hbv Infection ◽  
Liver Organoids

The effect of liver donors’ age, gender and metabolic state on pancreatic lineage activation

2021 ◽  
Vol 16 (1) ◽  
pp. 19-31
Author(s):  
Ioan V Matei ◽  
Irit Meivar-Levy ◽  
Daniela Lixandru ◽  
Simona Dima ◽  
Ioana R Florea ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Human Liver ◽  
Liver Cells ◽  
Diabetic Patients ◽  
Metabolic State ◽  
Human Liver Cells ◽  
Metabolic States ◽  
Different Ages ◽  
Liver Donors

Autologous cells replacement therapy by liver to pancreas transdifferentiation (TD) allows diabetic patients to be also the donors of their own therapeutic tissue. Aim: To analyze whether the efficiency of the process is affected by liver donors’ heterogeneity with regard to age, gender and the metabolic state. Materials & methods: TD of liver cells derived from nondiabetic and diabetic donors at different ages was characterized at molecular and cellular levels, in vitro. Results: Neither liver cells proliferation nor the propagated cells TD efficiency directly correlate with the age (3–60 years), gender or the metabolic state of the donors. Conclusion: Human liver cells derived from a wide array of ages and metabolic states can be used for autologous cells therapies for diabetics.

SAT-179-Human liver organoids culture as a novel in vitro model of HBV infection

2019 ◽  
Vol 70 (1) ◽  
pp. e708
Author(s):  
Chuan Kok Lim ◽  
Bang M Tran ◽  
Byron Shue ◽  
Nicholas Eyre ◽  
Dustin Flanagan ◽  
...  
Keyword(s):  
Human Liver ◽  
In Vitro Model ◽  
Hbv Infection ◽  
Vitro Model ◽  
Liver Organoids

Protective effects of papaya extracts on tert-butyl hydroperoxide mediated oxidative injury to human liver cells (An in-vitro study)

2012 ◽  
Vol 2 (3) ◽  
pp. 10-19 ◽  
Author(s):  
Sheri-Ann Tan ◽  
Sonia Ramos ◽  
María Angeles Martin ◽  
Raquel Mateos ◽  
Michael Harvey ◽  
...  
Keyword(s):  
Human Liver ◽  
In Vitro Study ◽  
Oxidative Injury ◽  
Liver Cells ◽  
Vitro Study ◽  
Protective Effects ◽  
Butyl Hydroperoxide ◽  
Human Liver Cells ◽  
Tert Butyl Hydroperoxide

scholarly journals Improvement of therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet

2020 ◽  
Author(s):  
Yu Na Lee ◽  
Hye-Jin Yi ◽  
Eun Hye Seo ◽  
Jooyun Oh ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Human Liver ◽  
Cell Sheet ◽  
Liver Cells ◽  
Cell Sheets ◽  
Human Liver Cells ◽  
Insulin Producing Cells ◽  
Differentiation Efficiency

Abstract Background: Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheets formation could improve differentiation efficiency and graft survival.Methods: Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1 and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency were confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPCs suspension was injected by portal vein (PV), and IPCs sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation and hepatotoxicity with IPCs injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging.Results: Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. One and two weeks following IPC sheet transplantation, immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin.Conclusions: In conclusion, cell sheet formation enhanced the differentiation function and maturation of IPCs in vitro. Additionally, parameters for clinical application such as distribution, therapeutic efficacy, and toxicity were favorable. The cell sheet technique may be used with IPCs derived from various cell sources in clinical applications.

Cytotoxicity evaluation of the alkaloid govaniadinein human liver cells and in vitro glucuronidation by liver microsomes

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
LMM Marques ◽  
U Rottkord ◽  
I Krug ◽  
M Behrens ◽  
A Adhikari ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Liver Cells ◽  
Human Liver Cells

scholarly journals Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

Toxins ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 2 ◽  
Author(s):  
Jee Eun Yoon ◽  
Kwang Yong Lee ◽  
Jin Sil Seok ◽  
Wei Nee Cheng ◽  
Hyuk Cheol Kwon ◽  
...  
Keyword(s):  
Phase I ◽  
Er Stress ◽  
Human Liver ◽  
Fusarium Species ◽  
Control Level ◽  
Liver Cells ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Eif2α Phosphorylation ◽  
Human Livers

Zearalenone (ZEN) is a mycotoxin produced by Fusarium species; however, its mechanisms of action in human livers have not been fully elucidated. Thus, we investigated the toxic mechanisms of ZEN in human liver cells. HepG2 cells were treated with ZEN (0–40 μg/mL) for up to 24 h. A significant decrease in cell viability was observed after treatment with 20 and 40 μg/mL of ZEN, including a significant increase in apoptosis and reactive oxygen species production. ZEN increased GRP78 and CHOP, and eIF2α phosphorylation, indicating ER stress; elevated transcription of the autophagy-associated genes, beclin1 and LC3, and translation of LC3; and increased phase I metabolism by increasing PXR and CYP3A4. The protein expression level of CYP3A4 was higher with ZEN treatment up to 20 μg/mL, but remained at the control level after treatment with 40 μg/mL ZEN. In phase II metabolism, Nrf2 activation and UGT1A expression were increased with ZEN treatment up to 20 μg/mL. Treating cells with an ER stress inhibitor alleviated ZEN-induced cell death and autophagy, and inhibited the expression of phase I/II enzymes. Overall, high ZEN concentrations can modulate the expression of phase I/II enzymes via ER stress and reduced protein levels in human liver cells.

Pharmacogenetic Determinants of Human Liver Microsomal Alfentanil Metabolism and the Role of Cytochrome P450 3A5

2005 ◽  
Vol 102 (3) ◽  
pp. 550-556 ◽  
Author(s):  
Theresa Mariero Klees ◽  
Pamela Sheffels ◽  
Kenneth E. Thummel ◽  
Evan D. Kharasch
Keyword(s):  
Human Liver ◽  
Interindividual Variability ◽  
Poor Correlation ◽  
Extensive Metabolism ◽  
Metabolite Ratio ◽  
Cytochrome P450 3A5 ◽  
Human Livers

Background There is considerable unexplained interindividual variability in the clearance of alfentanil. Alfentanil undergoes extensive metabolism by cytochrome P4503A4 (CYP3A4). CYP3A5 is structurally similar to CYP3A4 and metabolizes most CYP3A4 substrates but is polymorphically expressed. Livers with the CYP3A5*1 allele contain higher amounts of the native CYP3A5 protein than livers homozygous for the mutant CYP3A5*3 allele. This investigation tested the hypothesis that alfentanil is a substrate for CYP3A5 and that CYP3A5 pharmacogenetic variability influences human liver alfentanil metabolism. Methods Alfentanil metabolism to noralfentanil and N-phenylpropionamide was determined in microsomes from two groups of human livers, characterized for CYP3A4 and CYP3A5 protein content: low CYP3A5 (2.0-5.2% of total CYP3A, n = 10) and high CYP3A5 (46-76% of total CYP3A, n = 10). Mean CYP3A4 content was the same in both groups. The effects of the CYP3A inhibitors troleandomycin and ketoconazole, the latter being more potent toward CYP3A4, on alfentanil metabolism were also determined. Results In the low versus high CYP3A5 livers, respectively, noralfentanil formation was 77 +/- 31 versus 255 +/- 170 pmol . min . mg, N-phenylpropionamide formation was 8.0 +/- 3.1 versus 20.5 +/- 14.0 pmol . min . mg, and the metabolite ratio was 9.5 +/- 0.4 versus 12.7 +/- 1.4 (P &lt; 0.05 for all). There was a poor correlation between alfentanil metabolism and CYP3A4 content but an excellent correlation when CYP3A5 (i.e., total CYP3A content) was considered (r = 0.81, P &lt; 0.0001). Troleandomycin inhibited alfentanil metabolism similarly in the low and high CYP3A5 livers; ketoconazole inhibition was less in the high CYP3A5 livers. Conclusion In microsomes from human livers expressing the CYP3A5*1 allele and containing higher amounts of CYP3A5 protein, compared with those with the CYP3A5*3 allele and little CYP3A5, there was greater alfentanil metabolism, metabolite ratios more closely resembled those for expressed CYP3A5, and inhibitors with differing CYP3A4 and CYP3A5 selectivities had effects resembling those for expressed CYP3A5. Therefore, alfentanil is metabolized by human liver microsomal CYP3A5 in addition to CYP3A4, and pharmacogenetic variability in CYP3A5 expression significantly influences human liver alfentanil metabolism in vitro. Further investigation is warranted to assess whether the CYP3A5 polymorphism is a factor in the interindividual variability of alfentanil metabolism and clearance in vivo.

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