title: Magnetization transfer contrast MRI for non-invasive assessment of innate and adaptive immune responses against alginate-encapsulated cells.
abstract: By means of physical isolation of cells inside semi-permeable hydrogels, encapsulation has been widely used to immunoprotect transplanted cells. While spherical alginate microcapsules are now being used clinically, there still is little known about the patient's immune system response unless biopsies are obtained. We investigated the use of Magnetization Transfer (MT) imaging to non-invasively detect host immune responses against alginate capsules containing xenografted human hepatocytes in four groups of animals, including transplanted empty capsules (-Cells/-IS), capsules with live cells with (+LiveCells/+IS) and without immunosuppression (+LiveCells/-IS), and capsules with apoptotic cells in non-immunosuppressed animals (+DeadCells/-IS). The highest MT ratio (MTR) was found in +LiveCells/-IS, which increased from day 0 by 38% and 53% on days 7 and 14 after transplantation respectively, and corresponded to a distinctive increase in cell infiltration on histology. Furthermore, we show that macromolecular ratio maps based on MT data are more sensitive to cell infiltration and fibrosis than conventional MTR maps. Such maps showed a significant difference between +LiveCells/-IS (0.18 ± 0.02) and +DeadCells/-IS (0.13 ± 0.02) on day 7 (P < 0.01) existed, which was not observed on MTR imaging. We conclude that MT imaging, which is clinically available, can be applied for non-invasive monitoring of the occurrence of a host immune response against encapsulated cells.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Center of Nanomedicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Baltimore, MD 21205, USA.
authors.forename: Kannie W Y
authors.initials: KW
authors.lastname: Chan
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
authors.forename: Guanshu
authors.initials: G
authors.lastname: Liu
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van Zijl
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Baltimore, MD 21205, USA.
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Center of Nanomedicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: mtmcmaho@gmail.com.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D018914:Cells, Immobilized / Q000166:cytology / Q000187:drug effects; D020723:Glucuronic Acid / Q000494:pharmacology; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D046911:Macromolecular Substances / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008807:Mice, Inbred BALB C; D013194:Staining and Labeling
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D046911:Macromolecular Substances; D020723:Glucuronic Acid
keywords: Alginate microcapsules; Cellular imaging; Immune response; MRI; Molecular imaging