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Ultra-high-field MRI real-time imaging of HSC engraftment of the bone marrow niche

Leukemia volume 25, pages 1223–1231 (2011)Cite this article

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Abstract

The bone marrow (BM) undergoes extensive remodeling following irradiation damage. A crucial part of restoring homeostasis following irradiation is the ability of hematopoietic stem cells (HSCs) to home to and engraft specialized niches within the BM through a remodeling BM vascular system. Here we show that a combination of ultra-high-field strength magnetic resonance imaging (17.6 T, MRI) coupled with fluorescent microscopy (FLM) serves as a powerful tool for the in vivo imaging of cell homing within the BM. Ultra-high-field MRI can achieve high-resolution three-dimensional (3D) images (28 × 28 × 60 μm3) of the BM in live mice, sufficient to resolve anatomical changes in BM microstructures attributed to radiation damage. Following intra-arterial infusion with dsRed-expressing BM cells, labeled with superparamagnetic iron oxides, both FLM and MRI could be used to follow initial homing and engraftment of donor HSC to a limited number of preferred sites within a few cell diameters of the calcified bone—the endosteal niche. Subsequent histology confirmed the fidelity and accuracy of MRI to create non-invasive, high-resolution 3D images of donor cell engraftment of the BM in living animals at the level of single-cell detection.

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Acknowledgements

MRI was performed in the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) facility in the McKnight Brain Institute at the University of Florida, which is supported by the National High Field Magnet Laboratories. This work was supported by Grants RO1s HL7528 and HL70738 (NIH) to EWS and EEC-0506560 (NSF) to GAW and EWS. This work was supported by Grants RO1 HL75258 and HL70738 (NIH) to EWS and EEC-0506560 (NSF) to GAW and EWS. NEB performed or contributed to all experiments under advice from GAW and EWS. SK helped perform the SKL isolation, labeling and transplant experiments. LL helped perform the tibia bone window installations and acquired fluorescent videos of initial cell homing. All authors contributed equally in writing the paper.

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Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology, Program in Stem Cell Biology and Regenerative Medicine, University of Florida, Gainesville, FL, USA

    N E Bengtsson, S Kim, L Lin, G A Walter & E W Scott

  2. Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA

    G A Walter

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  1. N E Bengtsson
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  2. S Kim
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  3. L Lin
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  4. G A Walter
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Correspondence to E W Scott.

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Bengtsson, N., Kim, S., Lin, L. et al. Ultra-high-field MRI real-time imaging of HSC engraftment of the bone marrow niche. Leukemia 25, 1223–1231 (2011). https://doi.org/10.1038/leu.2011.72

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