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First published online August 9, 2007
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2007-0216v1
25/11/2936    most recent
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Submitted on March 26, 2007
Accepted on July 31, 2007

TECHNOLOGY DEVELOPMENT

Non-invasive Tracking of Cardiac Embryonic Stem Cells in vivo using Magnetic Resonance Imaging Techniques

Steven N. Ebert 1*, David G. Taylor 1, Ha Long Nguyen 1, David P. Kodack 2, Ronald J. Beyers 3, Yaqin Xu 3, Zequan Yang 3, Brent A. French 3

1 Biomolecular Science Center, University of Central Florida, Orlando, FL
2 Department of Pharmacology, Georgetown University Medical Center, Washington, DC
3 Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, VA

* To whom correspondence should be addressed. E-mail: ebert{at}mail.ucf.edu.


   Abstract

Despite rapid advances in the stem cell field, there is limited ability to identify and "track" transplanted or migrating stem cells in vivo. To overcome this limitation, we utilized magnetic resonance imaging (MRI) to detect and follow transplanted stem cells over a period of 28 days in mice using an established myocardial infarction (MI) model. Pluripotent mouse embryonic stem (mES) cells were expanded and induced to differentiate into beating cardiomyocytes in vitro. The cardiac-differentiated mES cells were then loaded with superparamagnetic fluorescent microspheres (1.63 µm diameter) and transplanted into ischemic myocardium immediately following ligation and subsequent reperfusion of the left anterior descending (LAD) coronary artery. To identify the transplanted stem cells in vivo, MRI was performed using a Varian Inova 4.7 Tesla scanner. Our results show that (i) the cardiac-differentiated mES were effectively loaded with superparamagnetic microspheres in vitro, (ii) the microsphere-loaded mES cells continued to beat in culture prior to transplantation, (iii) the transplanted mES cells were readily detected in the heart in vivo using non-invasive MRI techniques, (iv) the transplanted stem cells were detected in ischemic myocardium for the entire 28-day duration of the study as confirmed by MRI and postmortem histological analyses, and (v) concurrent functional MRI indicated typical loss of cardiac function, though significant amelioration of remodeling was noted after 28 days in hearts that received transplanted stem cells. These results demonstrate that it is feasible to simultaneously track transplanted stem cells and monitor cardiac function in vivo over an extended period using non-invasive MRI techniques.

Key Words. Cell transplantation, In vivo tracking, Mouse, Embryonic stem cells, Heart




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