Stem cells bear great promise for treatment of myocardial infarctions. Before this therapy becomes a reality in the clinics, in vivo studies using animal models are necessary to address important questions such as 1) whether the microenvironment in which stem cells are grafted provides enough stimuli for them to differentiate into cardiac myocytes, 2) whether adult stem cells (e.g. bone marrow derived mesenchymal stem cells) in addition to embryonic stem cells can undergo a full cardiogenic differentiation, 3) to what extent after grafting, the cardiac functions can be stabilized or improved. To address the above questions, this project will develop a non-invasive imaging system that allows repetitive, in vivo monitoring of the fate of stem cells and assessment of their potential therapeutic effect. By utilizing cardiac specific marker genes detectable by imaging, we will test whether the microenvironment into which stem cells are grafted provides enough cues for them to differentiate into the target tissue (i.e., cardiac muscle cells). By developing cine-based tagged MR imaging techniques, changes of regional myocardial contractile function resulted from the stem cell grafting will be assessed non-invasively. Finally, developing these imaging techniques on a murine myocardial infarct model allows the utilization of transgenic or knockout mouse models in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB002473-01
Application #
6725600
Study Section
Special Emphasis Panel (ZRG1-SSS-M (58))
Program Officer
Kelley, Christine A
Project Start
2003-09-20
Project End
2005-08-31
Budget Start
2003-09-20
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$237,750
Indirect Cost
Name
University of Pennsylvania
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Zhang, Hualei; Qiao, Hui; Ferrari, Victor A et al. (2012) Imaging Cell Therapy for Myocardial Regeneration. Curr Cardiovasc Imaging Rep 5:53-59
Qiao, Hui; Zhang, Hualei; Yamanaka, Satoshi et al. (2011) Long-term improvement in postinfarct left ventricular global and regional contractile function is mediated by embryonic stem cell-derived cardiomyocytes. Circ Cardiovasc Imaging 4:33-41
Boheler, Kenneth R; Joodi, Robert N; Qiao, Hui et al. (2011) Embryonic stem cell-derived cardiomyocyte heterogeneity and the isolation of immature and committed cells for cardiac remodeling and regeneration. Stem Cells Int 2011:214203
Zhang, Hualei; Qiao, Hui; Bakken, Ashley et al. (2011) Utility of dual-modality bioluminescence and MRI in monitoring stem cell survival and impact on post myocardial infarct remodeling. Acad Radiol 18:3-12
Qiao, Hui; Zhang, Hualei; Zheng, Yuanjie et al. (2009) Embryonic stem cell grafting in normal and infarcted myocardium: serial assessment with MR imaging and PET dual detection. Radiology 250:821-9
Qiao, Hui; Surti, Suleman; Choi, Seok Rye et al. (2009) Death and proliferation time course of stem cells transplanted in the myocardium. Mol Imaging Biol 11:408-14
Shen, Dinggang; Liu, Dengfeng; Cao, Zixiong et al. (2007) Coregistration of magnetic resonance and single photon emission computed tomography images for noninvasive localization of stem cells grafted in the infarcted rat myocardium. Mol Imaging Biol 9:24-31
Zhou, Rong; Acton, Paul D; Ferrari, Victor A (2006) Imaging stem cells implanted in infarcted myocardium. J Am Coll Cardiol 48:2094-106
Acton, Paul D; Thomas, Daniel; Zhou, Rong (2006) Quantitative imaging of myocardial infarct in rats with high resolution pinhole SPECT. Int J Cardiovasc Imaging 22:429-34
Thomas, D; Dumont, C; Pickup, S et al. (2006) T1-weighted cine FLASH is superior to IR imaging of post-infarction myocardial viability at 4.7T. J Cardiovasc Magn Reson 8:345-52

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