Schulze S, Keshvari S, Miller GC, Bridle KR, Hume DA, Irvine KM. Perisurgical colony stimulating factor one treatment ameliorates liver ischaemia/reperfusion injury in rats. World J Gastroenterol 2025; 31(24): 108234 [DOI: 10.3748/wjg.v31.i24.108234]
Corresponding Author of This Article
Katharine M Irvine, PhD, Associate Professor, Translational Research Institute, Mater Research Institute-University of Queensland, 37 Kent Street, Woolloongabba, Brisbane 4102, Queensland, Australia. katharine.irvine@uq.edu.au
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jun 28, 2025; 31(24): 108234 Published online Jun 28, 2025. doi: 10.3748/wjg.v31.i24.108234
Perisurgical colony stimulating factor one treatment ameliorates liver ischaemia/reperfusion injury in rats
Sarah Schulze, Sahar Keshvari, Gregory C Miller, Kim R Bridle, David A Hume, Katharine M Irvine
Sarah Schulze, Sahar Keshvari, David A Hume, Katharine M Irvine, Translational Research Institute, Mater Research Institute-The University of Queensland, Brisbane 4102, Queensland, Australia
Gregory C Miller, Envoi Pathology, Envoi Pathology, Brisbane 4000, Queensland, Australia
Kim R Bridle, Gallipoli Medical Research Institute, The University of Queensland, Greenslopes Private Hospital, Brisbane 4120, Queensland, Australia
Author contributions: Schulze S and Irvine KM were responsible for conceptualization; Schulze S, Keshvari S, Miller GC, Bridle KR, and Irvine KM were responsible for methodology, data collection and analysis; Schulze S and Irvine KM were responsible for draft manuscript; all authors were responsible for manuscript editing and review.
Supported by the German Research Foundation (Deutsche Forschungsgemeinschaft); and the Australian National Health and Medical Research Council and the Mater Foundation.
Institutional review board statement: The study was reviewed and approved by the University of Queensland Institutional Review Board (Approval No. IBC/1397/MRI/TRI/2022).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Queensland (Approval No. 2021_AE000958).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Katharine M Irvine, PhD, Associate Professor, Translational Research Institute, Mater Research Institute-University of Queensland, 37 Kent Street, Woolloongabba, Brisbane 4102, Queensland, Australia. katharine.irvine@uq.edu.au
Received: April 9, 2025 Revised: May 4, 2025 Accepted: June 4, 2025 Published online: June 28, 2025 Processing time: 79 Days and 1.1 Hours
Abstract
BACKGROUND
In the context of hepatobiliary and liver transplant surgery, ischemia-reperfusion (I/R) injury can occur due to temporary interruption of blood flow to the organ followed by a potentially damaging inflammatory response to reperfusion. Macrophages can drive inflammation in response to injury, but they can also promote liver growth and resolution of chronic liver injury and fibrosis. In chronic liver injury models in mice, macrophage colony stimulating factor (CSF)1 stimulates pro-regenerative macrophages.
AIM
To determine whether stimulation of macrophages with macrophage CSF could promote liver repair after I/R injury.
METHODS
We investigated the impact of perisurgical treatment with a long-circulating CSF1-Fc conjugate on liver injury and hepatocyte proliferation after 70% ischemia for 60 minutes at 6 hours, 48 hours and 7 days post reperfusion in rats. Circulating and liver tissue monocyte and macrophage subsets in the ischaemic and oxygenated lobes were assessed using quantitative PCR and flow cytometry.
RESULTS
CSF1-Fc treatment did not affect the extent of hepatocellular injury post-reperfusion, as indicated by serum transaminases. Liver I/R injury, especially necrotic area, was reduced in CSF1-Fc-treated rats 48 h post-surgery. This was associated with increased accumulation of macrophages in both the oxygenated and ischemic lobes (ILs), and peri-necrotic zone localization in the IL. CSF1-Fc treatment also promoted liver growth, associated with increased parenchymal and non-parenchymal cell proliferation. CSF1-Fc increased the abundance of CD43+ non-classical monocytes, consistent with the role of CSF1 signaling in monocyte maturation, and increased CD163 expression on mature macrophages.
CONCLUSION
This study suggests CSF1 stimulation drives monocytes/macrophages towards a pro-regenerative response and perisurgical CSF1 treatment might augment liver regeneration in patients undergoing liver resection.
Core Tip: During liver surgery, temporary interruption of blood flow followed by reperfusion can lead to tissue damage and inflammation. Macrophages and recruited monocytes can contribute to tissue damage and inflammation, but they are also necessary for injury resolution and prevention of post-operative infections. We show that perisurgical administration of the macrophage growth factor colony stimulating factor 1 promotes the accumulation of CD163+ pro-regenerative macrophages, reduces ischemia reperfusion-induced necrosis, and promotes liver growth in rats.
