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On the Use of Micron-Sized Iron Oxide Particles (MPIOS) to Label Resting Monocytes in Bone Marrow

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Abstract

Purpose

The use of MRI to monitor immune cell infiltration into various pathologies is well established. In an effort to boost the magnetic material within immune cells, this work attempted to label resting monocytes within bone marrow, in mice, by intravenous administration of micron-sized iron oxide particles (MPIOs), similar in fashion to the administration of (U)SPIO.

Procedures

MPIOs were incubated with various immune cells both in culture, and in whole blood. Flow cytometry and histology were used to analyze magnetic cell labeling. Also, MPIOs were injected intravenously into mice. In vivo, high-resolution 3-D MRI was performed on mouse legs, and signal changes were quantified. Flow cytometry and histology were used to analyze magnetic cell labeling of bone marrow resident cells.

Results

It is demonstrated here that monocytes and neutrophils can indeed endocytose MPIOs both in cell culture and ex vivo in whole blood. However, despite rapid accumulation of MPIOs within the bone marrow following injection, MPIOs did not label monocytes or any other hematopoietic cell type in the marrow. Hypotheses are drawn to explain these results in light of recent usage of MPIOs for immune cell tracking.

Conclusions

Systemic administration of various MPIO formulations showed that MPIOs arrive in bone marrow rapidly following injection and remain there for at least 7 days. Data also shows slow clearance of some particles from the tissue over this period. While MPIOs can efficiently label monocytes in culture and in whole blood ex vivo, they were not found to label bone marrow resident monocytes.

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Acknowledgement

Dr. Mark Horowitz, Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, is acknowledged for teaching us many of the biological procedures described herein, as well as for allowing us to perform the bone sectioning and histology in his laboratory. Dr. Menachem Elimelech, Chemical Engineering, Yale University, is acknowledged for providing us access to the Zeta PALS system. Dr. Diane Krause, Department of Laboratory Medicine, Yale University School of Medicine, is thanked for providing us access to a cytospin. Support received by National Institutes of Health grants DP2 OD004362, P30 NS052519, and P30 DK072442, and the Dana Foundation.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Diagnostic Radiology, Yale University School of Medicine, 300 Cedar Street, PO Box 208043, New Haven, CT, 06520-8043, USA

    Erik M. Shapiro

  2. Department of Biomedical Engineering, Yale University School of Medicine, New Haven, CT, USA

    Kevin S. Tang, Bradley Hann & Erik M. Shapiro

Authors
  1. Kevin S. Tang
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  2. Bradley Hann
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  3. Erik M. Shapiro
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Correspondence to Erik M. Shapiro.

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Tang, K.S., Hann, B. & Shapiro, E.M. On the Use of Micron-Sized Iron Oxide Particles (MPIOS) to Label Resting Monocytes in Bone Marrow. Mol Imaging Biol 13, 819–824 (2011). https://doi.org/10.1007/s11307-010-0437-3

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