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  • Review Article
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Molecular MRI of hematopoietic stem-progenitor cells: in vivo monitoring of gene therapy and atherosclerosis

Nature Clinical Practice Cardiovascular Medicine volume 5, pages 396–404 (2008)Cite this article

Abstract

A characteristic feature of atherosclerotic cardiovascular disease is the diffuse involvement of arteries across the entire human body and the presence of multiple, simultaneous lesions. The diffuse nature of this disease creates a unique challenge for early diagnosis and effective treatment. We believe that recent progress in the field of molecular MRI has opened new avenues towards solving the problem. A new technology has been developed that uses molecular MRI to monitor the migration and homing of hematopoietic stem-progenitor cells to injured arteries and atherosclerosis. In this Review, we introduce several novel technical developments in the field of molecular MRI of atherosclerosis, including advanced techniques for magnetic labeling of stem-progenitor cells and molecular MRI of hematopoietic bone marrow cells migrating to injured arteries and homing to atherosclerotic plaques. In addition, we examine molecular MRI of vascular gene therapy mediated by stem-progenitor cells. These new techniques provide the basis for the further development of in vivo MRI techniques to monitor stem-cell-mediated vascular gene therapy for multiple and diffuse atherosclerotic cardiovascular lesions.

Key Points

  • In this Review, we introduce several novel technical developments in the field of molecular MRI of atherosclerosis

  • Superparamagnetic particles have been developed that produce strong signal-altering properties during MRI, meaning that cells labeled with these magnetic resonance contrast agents can be visualized by MRI

  • Methods for cell uptake of contrast agents include simple incubation, use of the 'gene gun', magnetoelectroporation and magnetosonoporation

  • The techniques can be used for magnetic labeling of stem-progenitor cells, molecular MRI of hematopoietic stem-progenitor cells migrating to injured arteries and homing to atherosclerotic plaques, and molecular MRI of vascular gene therapy mediated by stem-progenitor cells

  • These efforts have opened new avenues for the effective management of atherosclerotic cardiovascular disease

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Figure 1: Magnetic resonance cell labeling using the simple incubation approach.
Figure 2: Cell labeled with Feridex I. V.® (AMAG Pharmaceuticals Inc., Cambridge, MA) using magnetosonoporation.
Figure 3: Localization and distribution of migrated lacZ-positive or GFP-positive cells in the thickened adventitia or neointimal hyperplasia of injured and control arteries.
Figure 4: The experimental protocol for molecular MRI of BM cells migrating to the sites of injured arteries.
Figure 5: In vivo MRI and corresponding histological findings from Feridex I. V.® (AMAG Pharmaceuticals Inc., Cambridge, MA)-labeled bone marrow cells and controls.
Figure 6: Fluorescent microscopic images of dual transfer of a reporter gene (GFP) and a T1 magnetic resonance contrast agent (motexafin gadolinium).

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Acknowledgements

This Review was supported by NIH grant HL078672. Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. Department of Radiology, B Qiu is Assistant Professor, and X Yang is Professor of Radiology and Director, at the Image-Guided Bio-Molecular Interventions Section, University of Washington School of Medicine, Seattle, WA, USA.,

    Bensheng Qiu & Xiaoming Yang

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Correspondence to Xiaoming Yang.

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The authors declare no competing financial interests.

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Qiu, B., Yang, X. Molecular MRI of hematopoietic stem-progenitor cells: in vivo monitoring of gene therapy and atherosclerosis. Nat Rev Cardiol 5, 396–404 (2008). https://doi.org/10.1038/ncpcardio1217

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