title: Quantitative Magnetic Particle Imaging Monitors the Transplantation, Biodistribution, and Clearance of Stem Cells In Vivo.
abstract: Stem cell therapies have enormous potential for treating many debilitating diseases, including heart failure, stroke and traumatic brain injury. For maximal efficacy, these therapies require targeted cell delivery to specific tissues followed by successful cell engraftment. However, targeted delivery remains an open challenge. As one example, it is common for intravenous deliveries of mesenchymal stem cells (MSCs) to become entrapped in lung microvasculature instead of the target tissue. Hence, a robust, quantitative imaging method would be essential for developing efficacious cell therapies. Here we show that Magnetic Particle Imaging (MPI), a novel technique that directly images iron-oxide nanoparticle-tagged cells, can longitudinally monitor and quantify MSC administration in vivo. MPI offers near-ideal image contrast, depth penetration, and robustness; these properties make MPI both ultra-sensitive and linearly quantitative. Here, we imaged, for the first time, the dynamic trafficking of intravenous MSC administrations using MPI. Our results indicate that labeled MSC injections are immediately entrapped in lung tissue and then clear to the liver within one day, whereas standard iron oxide particle (Resovist) injections are immediately taken up by liver and spleen. Longitudinal MPI-CT imaging also indicated a clearance half-life of MSC iron oxide labels in the liver at 4.6 days. Finally, our ex vivo MPI biodistribution measurements of iron in liver, spleen, heart, and lungs after injection showed excellent agreement (R(2) = 0.943) with measurements from induction coupled plasma spectrometry. These results demonstrate that MPI offers strong utility for noninvasively imaging and quantifying the systemic distribution of cell therapies and other therapeutic agents.
authors.affiliation: 1. Department of Bioengineering, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.affiliation: 2. Institute of Medical Technology, Hamburg University of Technology, Hamburg, Germany.
authors.forename: Marc P
authors.initials: MP
authors.lastname: von See
authors.affiliation: 1. Department of Bioengineering, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Yu
authors.affiliation: 1. Department of Bioengineering, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Beliz
authors.initials: B
authors.lastname: Gunel
authors.affiliation: 1. Department of Bioengineering, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Kuan
authors.initials: K
authors.lastname: Lu
authors.affiliation: 3. Department of Chemical and Biomolecular Engineering, University of California at Berkeley, Berkeley, CA 94720, USA; 4. Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Tandis
authors.initials: T
authors.lastname: Vazin
authors.affiliation: 1. Department of Bioengineering, University of California at Berkeley, Berkeley, CA 94720, USA; 3. Department of Chemical and Biomolecular Engineering, University of California at Berkeley, Berkeley, CA 94720, USA; 4. Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Schaffer
authors.affiliation: 1. Department of Bioengineering, University of California at Berkeley, Berkeley, CA 94720, USA; 5. Magnetic Insight, Inc., Newark, CA 94560, USA.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Goodwill
authors.affiliation: 1. Department of Bioengineering, University of California at Berkeley, Berkeley, CA 94720, USA; 6. Department of Electrical Engineering and Computer Science, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Conolly
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D005290:Ferric Compounds / Q000032:analysis*; D006801:Humans; D008280:Magnetics; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D053758:Nanoparticles / Q000032:analysis; D011916:Rats, Inbred F344; D013194:Staining and Labeling; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide
keywords: Magnetic particle imaging; cell therapy tracking; mesenchymal stem cells; quantitative imaging