Negligible Oval Cell Proliferation Following Ischemia-Reperfusion Injury With and Without Partial Hepatectomy.
BACKGROUND
Hepatic oval cells proliferate to replace hepatocytes and restore liver function when hepatocyte proliferation is compromised or inadequate. Exposure to chemical carcinogens, severe liver steatosis, and partial hepatectomy has been used in animal models to demonstrate the role of oval cells in liver regeneration. Ischemia-reperfusion injury (IRI) causes hepatocellular damage and death in the absence of confounding chemical toxicity; however, oval cell induction by IRI has not been demonstrated in vivo. We examine oval cell induction following partial IRI.


METHODS
Wistar rats were subjected to 2 IRI protocols: 70% warm liver ischemia for 30 minutes followed by reperfusion or 70% warm liver ischemia for 30 minutes with partial hepatectomy of the nonischemic lobes followed by reperfusion. Liver injury was monitored by serum alanine aminotransferase (ALT) at 1 day and 7 days of reperfusion. Oval cell proliferation was monitored by indirect immunofluorescence staining using the surface markers BD.2 and Thy-1. Cellular proliferation was quantified by 5-ethynyl-2'-deoxyuridine (EdU) incorporation in vivo.


RESULTS
Serum ALT elevation was only observed at the 1-day time point in the IRI with partial hepatectomy model. Oval cell marker expression was restricted to the biliary structures in both the ischemic and the nonischemic control lobes. Oval cell induction, measured by changes in the frequency of BD.2 and Thy-1 expression and EdU incorporation, was not significantly altered by IRI.


CONCLUSIONS
In both mild and moderate IRI models, we did not find evidence of oval cell induction or proliferation. EdU staining was restricted to hepatocytes, suggesting that liver regeneration following IRI is mediated by hepatocyte proliferation.
Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA ; Department of General Surgery, Singapore General Hospital, Singapore.
Ek Khoon
EK
Tan
Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA.
Maureen
M
Shuh
Department of Pediatrics, Rhode Island Hospital and Brown University, Providence, RI.
Heather
H
Francois-Vaughan
Department of Pediatrics, Rhode Island Hospital and Brown University, Providence, RI ; Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Brown University, Providence, RI.
Jennifer A
JA
Sanders
Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA ; Multi-Organ Transplant Institute, Ochsner Clinic Foundation, New Orleans, LA ; The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA.
Ari J
AJ
Cohen
Hepatocytes; ischemia; liver; reperfusion