In vivo Cell Tracking Using Non-invasive Imaging of Iron Oxide-Based Particles with Particular Relevance for Stem Cell-B

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In vivo Cell Tracking Using Non-invasive Imaging of Iron Oxide-Based Particles with Particular Relevance for Stem Cell-Based Treatments of Neurological and Cardiac Disease Joel C. Glover ,1,2 Markus Aswendt,3 Jean-Luc Boulland,1,2 Jasna Lojk,4 Stefan Stamenković,5 Pavle Andjus,5 Fabrizio Fiori,6 Mathias Hoehn,3 Dinko Mitrecic,7 Mojca Pavlin,4,8 Stefano Cavalli,9 Caterina Frati,9 Federico Quaini,9 on behalf of the EU COST Action 16122 (BIONECA) 1

Laboratory for Neural Development and Optical Recording (NDEVOR), Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, PB 1105, Blindern, Oslo, Norway 2 Norwegian Center for Stem Cell Research, Oslo University Hospital, Oslo, Norway 3 Institut für Neurowissenschaften und Medizin, Forschungszentrum Jülich, Leo-Brandt-Str. 5, 52425, Jülich, Germany 4 Group for Nano and Biotechnological Applications, Faculty of Electrical Engineering, University of Ljubljana, Trzaska cesta 25, Ljubljana, Slovenia 5 Center for Laser Microscopy, Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, PB 52, 10001 Belgrade, Serbia 6 Department of Applied Physics, Università Politecnica delle Marche - Di.S.C.O., Via Brecce Bianche, 60131, Ancona, Italy 7 Laboratory for Stem Cells, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia 8 Institute of Biophysics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia 9 Department of Medicine and Surgery, University of Parma, Parma, Italy

Abstract Stem cell-based therapeutics is a rapidly developing field associated with a number of clinical challenges. One such challenge lies in the implementation of methods to track stem cells and stem cell-derived cells in experimental animal models and in the living patient. Here, we provide an overview of cell tracking in the context of cardiac and neurological disease, focusing on the use of iron oxide-based particles (IOPs) visualized in vivo using magnetic resonance imaging (MRI). We discuss the types of IOPs available for such tracking, their advantages and limitations, approaches for labeling cells with IOPs, biological interactions and effects of IOPs at the molecular and cellular levels, and MRI-based and associated approaches for in vivo and histological visualization. We conclude with reviews of the literature on IOP-based cell tracking in cardiac and neurological disease, covering both preclinical and clinical studies. Key words: Iron oxide, Stem cell, Cardiomyocytes, Neural progenitor cells, MRI, MION, SPIO, USPIO, MPIO, MPI, Micro-CT

Markus Aswendt, Jean-Luc Boulland, Jasna Lojk and Stefan Stamenković contributed equally to this work. Correspondence to: Joel Glover; e-mail: [email protected]

Glover J.C. et al.: Non-invasive In vivo Cell Tracking

Introduction The use of stem cells in regenerative medicine holds the promise of enabling the repair of tissues and organs, either directly through the replacement of cells lost due to acute inj