We are a collaborative and tightly knit group of investigators who wish to contribute to the CCTRN our expertise in 1) small molecules and stem cells in peripheral arterial disease (John Cooke);2) clinical device development in stem cell delivery, coronary artery disease, and structural heart disease (William Fearon, Robert Robbins, and Alan Yeung);3) multimodality cellular, molecular, and physiologic imaging of stem cells and ischemic cardiovascular diseases (Sanjiv Gambhir, Dwight Nishimura, Joseph Wu, and Phillip Yang);4) bone marrow stem cell harvest and processing (Robert Negrin);and 5) stem cell characterization (Garry Nolan). We propose to contribute a novel multi-modality approach to assess stem cell engraftment employing manganese enhanced MRI (MEMRI) by Phillip Yang, and stem cell localization utilizing lndium-111 cell labeling by Joe Wu and Sam Gambhir. In addition, we will contribute innovative methodology to evaluate tissue perfusion and peri-infarct viability using magnetic resonance imaging (MRI) algorithms developed by Dwight Nishimura and Phillip Yang for peripheral and myocardial imaging, respectively. Finally, we will provide a comprehensive definition of the CD34+ mononuclear cells (MNCs) to be used in our human studies, using the paradigm-changing technology of single cell mass cytometry recently developed at Stanford (Bendall SC et al. Science 2011). This new technology provides a platform for massively multiplexed measurements of single-cell biological parameters that can finely delineate cellular subsets. We intend to correlate these subsets with clinical endpoints in our PAD and CAD research protocols, to determine what cell subsets may be most critical for any observed benefit.

Public Health Relevance

Adult stem cell trials in patients with CAD PAD have shown promise. However, the effect size for most endpoints has been modest. The mechanism(s) of benefit remain poorly understood. We suggest that a better definition and imaging ofthe therapeutic cell population could yield insights that might improve our selection and administration of adult stem cells, and potentially improve therapeutic benefit.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
1UM1HL113456-01
Application #
8288408
Study Section
Special Emphasis Panel (ZHL1-CSR-O (F2))
Program Officer
Ebert, Ray F
Project Start
2012-03-23
Project End
2019-02-28
Budget Start
2012-03-23
Budget End
2013-02-28
Support Year
1
Fiscal Year
2012
Total Cost
$534,435
Indirect Cost
$180,398
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Chung, Wook-Jin; Cho, Ahryon; Byun, Kyunghee et al. (2016) Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function after severe myocardial injury. Int J Cardiol 222:361-7
Santoso, Michelle R; Yang, Phillip C (2016) Magnetic Nanoparticles for Targeting and Imaging of Stem Cells in Myocardial Infarction. Stem Cells Int 2016:4198790
Bhatnagar, Aruni; Bolli, Roberto; Johnstone, Brian H et al. (2016) Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Am Heart J 179:142-50
Mahmoudi, Morteza; Tachibana, Atsushi; Goldstone, Andrew B et al. (2016) Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes. Sci Rep 6:26960
Wei, Ke; Serpooshan, Vahid; Hurtado, Cecilia et al. (2015) Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature 525:479-85
Dash, Rajesh; Kim, Paul J; Matsuura, Yuka et al. (2015) Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model. J Am Heart Assoc 4:
Schutt, Robert C; Trachtenberg, Barry H; Cooke, John P et al. (2015) Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial. Circ Res 116:99-107
Kim, Paul J; Mahmoudi, Morteza; Ge, Xiaohu et al. (2015) Direct evaluation of myocardial viability and stem cell engraftment demonstrates salvage of the injured myocardium. Circ Res 116:e40-50
Cooke, John P; Chen, Zhen (2015) A compendium on peripheral arterial disease. Circ Res 116:1505-8
Cooke, John P; Losordo, Douglas W (2015) Modulating the vascular response to limb ischemia: angiogenic and cell therapies. Circ Res 116:1561-78

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