title: Monitoring of Liver Cell Transplantation in a Preclinical Swine Model Using Magnetic Resonance Imaging.
abstract: Liver cell transplantation (LCT) is a promising treatment approach for certain liver diseases, but clinical implementation requires methods for noninvasive follow-up. Labeling with superparamagnetic iron oxide particles can enable the detection of cells with magnetic resonance imaging (MRI). We investigated the feasibility of monitoring transplanted liver cells by MRI in a preclinical swine model and used this approach to evaluate different routes for cell application. Liver cells were isolated from landrace piglets and labeled with micron-sized iron oxide particles (MPIO) in adhesion. Labeled cells (n = 10), native cells (n = 3), or pure particles (n = 4) were transplanted to minipigs via intraportal infusion into the liver, direct injection into the splenic parenchyma, or intra-arterial infusion to the spleen. Recipients were investigated by repeated 3.0 Tesla MRI and computed tomography angiography up to 8 weeks after transplantation. Labeling with MPIO, which are known to have a strong effect on the magnetic field, enabled noninvasive detection of cell aggregates by MRI. Following intraportal application, which is commonly applied for clinical LCT, MRI was able to visualize the microembolization of transplanted cells in the liver that were not detected by conventional imaging modalities. Cells directly injected into the spleen were retained, whereas cell infusions intra-arterially into the spleen led to translocation and engraftment of transplanted cells in the liver, with significantly fewer microembolisms compared to intraportal application. These findings demonstrate that MRI can be a valuable tool for noninvasive elucidation of cellular processes of LCT and-if clinically applicable MPIO are available-for monitoring of LCT under clinical conditions. Moreover, the results clarify mechanisms relevant for clinical practice of LCT, suggesting that the intra-arterial route to the spleen deserves further evaluation.
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Nathanael
authors.initials: N
authors.lastname: Raschzok
authors.affiliation: † Radiology, Charité-Campus Mitte, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Teichgräber
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Billecke
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Zielinski
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Steinz
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Nora N
authors.initials: NN
authors.lastname: Kammer
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin, Berlin, Germany; ‡Visceral, Transplantation, Thorax, and Vascular Surgery, Universitätsklinikum Leipzig, Leipzig, Germany.
authors.forename: Mehmet H
authors.initials: MH
authors.lastname: Morgul
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schmeisser
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Michaela K
authors.initials: MK
authors.lastname: Adonopoulou
authors.affiliation: § Institute of Pathology, Charité-Campus Mitte, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Morawietz
authors.affiliation: ¶ Centre for Biomaterial Development and Berlin-Brandenburg Centre for Regenerative Therapies (BCRT), Institute for Polymer Research, GKSS Research Centre Geesthacht GmbH , Teltow , Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hiebl
authors.affiliation: # Department of Materials, ETH Zurich , Zurich , Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Schwartlander
authors.affiliation: * Cytonet GmbH , Weinheim , Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rüdinger
authors.affiliation: † Radiology, Charité-Campus Mitte, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Hamm
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Igor M
authors.initials: IM
authors.lastname: Sauer
keywords: Cell tracking; Iron oxide particle; Liver cell transplantation (LCT); Magnetic resonance imaging (MRI); Micron-sized iron oxide particles (MPIO)