{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:12:20Z","timestamp":1788307940667,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mesenchymal stromal cells (MSC) have been shown to mitigate IRI through their anti-inflammatory and immune-modulating capacities. This study aims to demonstrate the feasibility, safety, and effectiveness of hepatic administration of bone marrow-derived (BM)-MSCs in a large pig model relevant to human anatomy. After complete vascular exclusion for 45 min, 3 \u00d7 106 human BM-MSCs\/kg body weight were infused via the portal vein or hepatic artery. BM-MSC infusion did not cause obstruction of hepatic or pulmonary blood flow within 6 h after infusion. Cells were effectively retained in the liver, being undetectable in peripheral blood, lung, and spleen samples. Human B2M expression, as a marker for BM-MSC presence, was significantly higher for the left liver lobe in arterial infusion compared to portal infusion. In liver samples with high BM-MSC levels, we identified the prevention of up- or downregulation of some genes related to inflammation and energy metabolism that was present in non-treated control samples, indicating biological effects within 6 h of infusion. We conclude that hepatic BM-MSC infusion is feasible and safe, with the hepatic artery serving as the optimal administration route for homogenous distribution. These findings pave the way for clinical studies on MSC infusion in IRI, either in situ in liver conditions or ex situ during machine perfusion.<\/jats:p>","DOI":"10.3390\/cells14191496","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T07:46:49Z","timestamp":1758786409000},"page":"1496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimizing the Infusion Route of Human Bone Marrow Mesenchymal Stromal Cells to Mitigate Liver Ischemia\u2013Reperfusion Injury in a Porcine Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0348-5165","authenticated-orcid":false,"given":"Stefan H.","family":"Luijmes","sequence":"first","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Job P.","family":"van Kooten","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4422-3807","authenticated-orcid":false,"given":"Henk P.","family":"Roest","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7752-6532","authenticated-orcid":false,"given":"Jubi","family":"de Haan","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8611-840X","authenticated-orcid":false,"given":"Michail","family":"Doukas","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia J.","family":"Verhoeven","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kairong","family":"Wang","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-1279","authenticated-orcid":false,"given":"Jorke","family":"Willemse","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0651-5334","authenticated-orcid":false,"given":"Luc J. W.","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9908-6673","authenticated-orcid":false,"given":"Monique M. A.","family":"Verstegen","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1131-027X","authenticated-orcid":false,"given":"Jeroen","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.jhep.2013.06.017","article-title":"Hepatic ischemia and reperfusion injury: Effects on the liver sinusoidal milieu","volume":"59","author":"Peralta","year":"2013","journal-title":"J. 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