scholarly journals Progression of Repair and Injury in Human Liver Slices

2018 ◽  
Vol 19 (12) ◽  
pp. 4130
Author(s):  
Alison E.M. Vickers ◽  
Anatoly V. Ulyanov ◽  
Robyn L. Fisher
Keyword(s):  
Gene Expression ◽  
Human Liver ◽  
Wound Repair ◽  
Specific Gene ◽  
Drug Induced ◽  
Kidney Slices ◽  
Liver Slices ◽  
Liver And Kidney ◽  
Injury And Repair ◽  
Human Liver Slices

Human liver slice function was stressed by daily dosing of acetaminophen (APAP) or diclofenac (DCF) to investigate injury and repair. Initially, untreated human liver and kidney slices were evaluated with the global human U133A array to assess the extended culture conditions. Then, drug induced injury and signals of repair in human liver slices exposed to APAP or DCF (1 mM) were evaluated via specific gene expression arrays. In culture, the untreated human liver and kidney slices remained differentiated and gene expression indicated that repair pathways were activated in both tissues. Morphologically the human liver slices exhibited evidence of repair and regeneration, while kidney slices did not. APAP and DCF exposure caused a direct multi-factorial response. APAP and DCF induced gene expression changes in transporters, oxidative stress and mitochondria energy. DCF caused a greater effect on heat shock and endoplasmic reticulum (ER) stress gene expression. Concerning wound repair, APAP caused a mild repression of gene expression; DCF suppressed the expression of matrix collagen genes, the remodeling metalloproteases, cell adhesion integrins, indicating a greater hinderance to wound repair than APAP. Thus, human liver slices are a relevant model to investigate the mechanisms of drug-induced injury and repair.

Gene expression analysis of precision cut human liver slices indicate stable expression of ADME-Tox related genes

2010 ◽  
Vol 196 ◽  
pp. S215
Author(s):  
M. Elferink ◽  
P. Olinga ◽  
E. Van Leeuwen ◽  
S. Bauerschmidt ◽  
J. Polman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Human Liver ◽  
Gene Expression Analysis ◽  
Stable Expression ◽  
Liver Slices ◽  
Human Liver Slices

Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes

2011 ◽  
Vol 253 (1) ◽  
pp. 57-69 ◽  
Author(s):  
M.G.L. Elferink ◽  
P. Olinga ◽  
E.M. van Leeuwen ◽  
S. Bauerschmidt ◽  
J. Polman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Human Liver ◽  
Gene Expression Analysis ◽  
Stable Expression ◽  
Liver Slices ◽  
Human Liver Slices

Human Liver Slices to Investigate Injury and Repair

2018 ◽  
Vol 4 (3) ◽  
pp. 280-287 ◽  
Author(s):  
Alison E.M. Vickers ◽  
Robyn L. Fisher
Keyword(s):  
Human Liver ◽  
Liver Slices ◽  
Injury And Repair ◽  
Human Liver Slices

Cold- and Cryopreservation of Human Liver and Kidney Slices

Cryobiology ◽  
1993 ◽  
Vol 30 (3) ◽  
pp. 250-261 ◽  
Author(s):  
Robyn L. Fisher ◽  
Steven J. Hasal ◽  
Jeffery T. Sanuik ◽  
Katherine S. Scott ◽  
A.Jay Gandolfi ◽  
...  
Keyword(s):  
Human Liver ◽  
Kidney Slices ◽  
Liver And Kidney

Abstract 289: Transcriptomic Analysis of Inter- and Intra-patient Variation in Human iPSCs: Platform for Precision Medicine to Predict Drug Toxicity

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Elena Matsa ◽  
Paul W Burridge ◽  
Kun-Hsing Yu ◽  
Haodi Wu ◽  
Vittavat Termglinchan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Precision Medicine ◽  
Disease Modeling ◽  
Sendai Virus ◽  
Expression Profiles ◽  
Cardiac Differentiation ◽  
Patient Specific ◽  
Specific Gene ◽  
Drug Induced ◽  
Human Ipscs

Rapid improvements in human induced pluripotent stem cell (hiPSC) differentiation methodologies have allowed previously unattainable access to high-purity, patient-specific cardiomyocytes (CMs) for use in disease modeling, cardiac regeneration, and drug testing. In the present study, we investigate the ability of hiPSC-derived cardiomyocytes (hiPSC-CMs) to reflect the donor’s genetic identity and serve as preclinical functional readout platforms for precision medicine. We used footprint-free Sendai virus to create two separate hiPSC clones from the fibroblasts of five different individuals lacking known mutations associated with cardiovascular disease. Whole genome expression profiling of hiPSC-CMs showed that inter-patient variation was greater than intra-patient variation, thereby verifying that reprogramming and cardiac differentiation technologies can preserve patient-specific gene expression signatures. Gene ontologies (GOs) accounting for inter-patient variation were mostly metabolic or epigenetic. Toxicology analysis based on gene expression profiles predicted patient-specific susceptibility of hiPSC-CMs to cardiotoxicity, and functional assays using drugs targeting key regulators in pathways predicted to produce cardiotoxicity showed inter-patient differential responses in hiPSC-CMs. Our data suggest that hiPSC-CMs can be used in vitro to predict and help prevent patient-specific drug-induced cardiotoxicity, potentially enabling personalized patient consultation in the future.

Cryopreservation of pig and human liver slices

Cryobiology ◽  
1991 ◽  
Vol 28 (2) ◽  
pp. 131-142 ◽  
Author(s):  
Robyn Fisher ◽  
Charles W. Putnam ◽  
Lawrence J. Koep ◽  
I.Glenn Sipes ◽  
A.Jay Gandolfi ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Slices ◽  
Human Liver Slices

THE METABOLISM OF ALDOSTERONE BY SURVIVING DOG AND HUMAN LIVER SLICES

1960 ◽  
Vol 38 (1) ◽  
pp. 739-756
Author(s):  
Thomas Sandor ◽  
Wojciech J. Nowaczynski ◽  
Jacques Genest
Keyword(s):  
Human Liver ◽  
Chemical Characterization ◽  
Liver Slices ◽  
Metabolic Products ◽  
Reducing Substances ◽  
Dog Liver ◽  
Human Liver Slices ◽  
Acetate Form

Surviving dog liver slices were incubated with d,l-aldosterone-21-monoacetate, d,l-aldosterone, d-aldosterone, and d-aldosterone-21-C14. Human liver slices were incubated with d,l-aldosterone-21-monoacetate and d-aldosterone. The incubations were performed in a Krebs–Ringer–phosphate medium (pH 7.4), with 200 mg glucose added per 100 ml of medium, at a temperature of 37 °C. After incubation, the medium was extracted with chloroform and the crude extract extensively fractionated on column and paper chromatographic systems. In addition to free aldosterone, four metabolic products were isolated, two ring A reduced α-ketolic and two ultraviolet absorbing, non-reducing substances. The partial chemical characterization of these metabolites was attempted. The search for aldosterone metabolites in human urine resulted in the isolation of a substance in acetate form from the urine of a patient suffering from primary aldosteronism which may be identical with one of the ring A reduced metabolites obtained in the in vitro experiments.

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