title: Fate and Effect of Intravenously Infused Mesenchymal Stem Cells in a Mouse Model of Hepatic Ischemia Reperfusion Injury and Resection.
abstract: Liver ischemia reperfusion injury (IRI) is inevitable during transplantation and resection and is characterized by hepatocellular injury. Therapeutic strategies to reduce IRI and accelerate regeneration could offer major benefits. Mesenchymal stem cells (MSC) are reported to have anti-inflammatory and regeneration promoting properties. We investigated the effect of MSC in a model of combined IRI and partial resection in the mouse. Hepatic IRI was induced by occlusion of 70% of the blood flow during 60 minutes, followed by 30% hepatectomy. 2 × 10(5) MSC or PBS were infused 2 hours before or 1 hour after IRI. Six, 48, and 120 hours postoperatively mice were sacrificed. Liver damage was evaluated by liver enzymes, histology, and inflammatory markers. Regeneration was determined by liver/body weight ratio, proliferating hepatocytes, and TGF-β levels. Fate of MSC was visualized with 3D cryoimaging. Infusion of 2 × 10(5) MSC 2 hours before or 1 hour after IRI and resection showed no beneficial effects. Tracking revealed that MSC were trapped in the lungs and did not migrate to the site of injury and many cells had already disappeared 2 hours after infusion. Based on these findings we conclude that intravenously infused MSC disappear rapidly and were unable to induce beneficial effects in a clinically relevant model of IRI and resection.
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, Netherlands.
authors.forename: T C
authors.initials: TC
authors.lastname: Saat
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van den Engel
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Bijman-Lachger
authors.affiliation: Nephrology and Transplantation, Department of Internal Medicine, Erasmus University Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, Netherlands.
authors.forename: S S
authors.initials: SS
authors.lastname: Korevaar
authors.affiliation: Nephrology and Transplantation, Department of Internal Medicine, Erasmus University Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Hoogduijn
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, Netherlands.
authors.forename: J N M
authors.initials: JN
authors.lastname: IJzermans
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, Netherlands.
authors.forename: R W F
authors.initials: RW
authors.lastname: de Bruin