Molecular imaging is a new discipline that makes possible the noninvasive visualization of cellular and molecular processes in living subjects. Here we will adopt the reporter gene and reporter probe imaging technique (developed initially for cancer researchers) to solve a different important problem in cardiology (i.e., understand pharmacokinetics and biodistribution of cardiac stem cell therapy). In particular, we will develop and validate various reporter genes that will enable us to image fate of cardiac stem cells (CSC) in vivo. We will use clinical positron emission tomography and computed tomography (PET/CT) and magnetic resonance imaging (MRI) to track the survival, proliferation, and function of transplanted cells in pre-clinical large animal models. The information gathered from these studies should prove instrumental for marrying molecular imaging with clinical stem cell therapy in the future.

Public Health Relevance

Coronary artery disease (CAD) is a progressive disease with high morbidity and mortality rates in the US. Following myocardial infarction (MI), the limited ability of the surviving cardiac cells to proliferate renders the damaged heart susceptible to unfavorable remodeling processes and morbid sequelae such as heart failure. For now, heart transplantation is the only viable treatment option for end-stage heart failure patients. Given the persistent shortage of donor heart organs, stem cell therapy has emerged as a promising candidate for treating ischemic heart disease because it provides a virtually unlimited source of cardiomyocytes, endothelial cells, and other differentiated cell types to be used in all stages of cardiac repair. Thus, imaging cell fate after transplantation is a high priority in both basic research and clinical translation. In order for cell based therapy to truly succeed, we must be able to track the location(s) of delivered cells, the duration of cell survival, and any potential adverse effects. Our major goals for this grant are to develop and validate novel reporter gene &reporter probe techniques for tracking fate of cardiac stem cells (CSCs). Importantly, the information we obtain here on detection sensitivity and the overall experience we gain will be extremely valuable for eventual clinical translation of cardiac molecular imaging in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB009689-04
Application #
8435470
Study Section
Clinical Molecular Imaging and Probe Development (CMIP)
Program Officer
Hunziker, Rosemarie
Project Start
2010-05-01
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2013
Total Cost
$333,961
Indirect Cost
$130,018
Name
Stanford University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Riegler, Johannes; Gillich, Astrid; Shen, Qi et al. (2014) Cardiac tissue slice transplantation as a model to assess tissue-engineered graft thickness, survival, and function. Circulation 130:S77-86
Ong, Sang-Ging; Lee, Won Hee; Huang, Mei et al. (2014) Cross talk of combined gene and cell therapy in ischemic heart disease: role of exosomal microRNA transfer. Circulation 130:S60-9
Huber, Bruno C; Ransohoff, Julia D; Ransohoff, Katherine J et al. (2013) Costimulation-adhesion blockade is superior to cyclosporine A and prednisone immunosuppressive therapy for preventing rejection of differentiated human embryonic stem cells following transplantation. Stem Cells 31:2354-63
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Lee, Andrew S; Tang, Chad; Rao, Mahendra S et al. (2013) Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med 19:998-1004
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Yan, Xinrui; Ray, Pritha; Paulmurugan, Ramasamy et al. (2013) A transgenic tri-modality reporter mouse. PLoS One 8:e73580
Chen, Ian Y; Wu, Joseph C (2013) Molecular imaging: the key to advancing cardiac stem cell therapy. Trends Cardiovasc Med 23:201-10

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