In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis
Klara Kirschbaum, Jana K Sonner, Matthias W Zeller, Katrin Deumelandt, Julia Bode, Rakesh Sharma, Thomas Kruewel, Manuel Fischer, Angelika Hoffmann, Milene Costa da Silva, Martina U Muckenthaler, Wolfgang Wick, Bjoern Tews, John W Chen, Sabine Heiland, Martin Bendszus, Michael Platten, Michael O Breckwoldt
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2016
Innate immune cells play a key role in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted to visualizing secondary effects of inflammation, such as gliosis and blood-brain barrier disruption. Advanced molecular imaging, such as iron oxide nanoparticle imaging, can allow direct imaging of cellular and molecular activity, but the exact cell types that phagocytose nanoparticles in vivo and how phagocytic activity relates to disease severity is not well understood. In this study we used MRI to map inflammatory infiltrates using high-field MRI and fluorescently labeled cross-linked iron oxide nanoparticles for cell tr..View full abstract
Awarded by Deutsche Forschungsgemeinschaft
We thank Simon Becker for excellent technical assistance; Ralph Weissleder of the Massachusetts General Hospital, Harvard Medical School for providing CLIO nanoparticles and for helpful discussion of the manuscript; E. Neuwelt of the Oregon Health and Science University for the kind gift of ferumoxytol; and D. Krunic of the DKFZ Light Microscopy Facility for experimental support. This work was funded by grants from the Heidelberg University Innovation Fund FRONTIER (to M.P.) and by Deutsche Forschungsgemeinschaft Grant FOR2289: PL315/3-1 (to M.P). M.O.B. and A.H. were supported by a Physician-Scientist Fellowship of the Medical Faculty, University of Heidelberg. M.O.B. received funding from the Hoffmann-Klose Foundation (University of Heidelberg), the Novartis Foundation, and Neurowind e.V. J.K.S. was supported by the Helmholtz International Graduate School for Cancer Research at DKFZ, and K.D. was supported by the German Federal Ministry of Education and Research.