Next Article in Journal
Brain-Derived Neurotrophic Factor in Central Nervous System Myelination: A New Mechanism to Promote Myelin Plasticity and Repair
Next Article in Special Issue
Dual Role of Bile Acids on the Biliary Epithelium: Friend or Foe?
Previous Article in Journal
The Activity of Matrix Metalloproteinases (MMP-2, MMP-9) and Their Tissue Inhibitors (TIMP-1, TIMP-3) in the Cerebral Cortex and Hippocampus in Experimental Acanthamoebiasis
Previous Article in Special Issue
Isoquercetin Improves Hepatic Lipid Accumulation by Activating AMPK Pathway and Suppressing TGF-β Signaling on an HFD-Induced Nonalcoholic Fatty Liver Disease Rat Model
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle

Progression of Repair and Injury in Human Liver Slices

Human Translational Models LLC, Irvine, CA 92612, USA
Inova Translational Medicine Institute, Inova Hospital, Fairfax, VA 22031, USA
Vitron, Inc., Tucson, AZ 85747, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(12), 4130;
Received: 30 October 2018 / Revised: 3 December 2018 / Accepted: 18 December 2018 / Published: 19 December 2018
(This article belongs to the Special Issue Liver Damage and Repair)
PDF [2543 KB, uploaded 20 December 2018]


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. View Full-Text
Keywords: repair and injury; human liver slices repair and injury; human liver slices

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Vickers, A.E.M.; Ulyanov, A.V.; Fisher, R.L. Progression of Repair and Injury in Human Liver Slices. Int. J. Mol. Sci. 2018, 19, 4130.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top