Abstract

Project 3:
Specific Aim #1 : To assess efficacy of endogenous cardiac stem cells in a porcine model of acute ischemic cardiomyopathy. We will use our established swine model of anterior wall Ml to determine whether endogenous cardiac stem cells (CSCs) beneficially affect left ventricular remodeling in the setting of post-Mi ventricular dysfunction. The results of this study will define the efficacy and safety of CSCs in repairing acute scar formation and define the most effective method of CSC delivery (intracoronary infusion vs. intramyocardial injection) and CSC dose (cell numbers) for our human studies (Aims #2 and #3).
In Aim #2, we will assess the safety of autologous CSC therapy in patients with acute ischemic cardiomyopathy. This study will assess the safety of autologous CSC therapy in patients with a recent ST segment elevation myocardial infarction and resultant depressed left ventricular systolic function (EF<0.35) identified by MRI. Autologous CSCs will be harvested, propagated, and percutaneously implanted one month post-Mi and following automatic internal cardiodefibrillator (AICD) placement. Safety will be assessed by determining (a) clinical status;(b) arrhythmia potential (via Holter, AICD monitoring and interrogation, and EP study);and (c) LV function and infarct size over the 90 day follow up period.
Aim #3 : To assess efficacy of autologous CSC therapy in patients with acute ischemic cardiomyopathy. This randomized, placebo-controlled trial will determine the efficacy of CSC therapy in improving left ventricular function and remodeling and clinical status of patients with acute ischemic cardiomyopathy. Patients presenting with their first ST segment elevation Ml and left ventricular systolic dysfunction (EF<0.35) will be randomized to treatment with (a) autologous CSC or (b) placebo to be placed one month post-Mi and following AICD placement. Efficacy (improvement in left ventricular function and remodeling), clinical benefit, and safety will be assessed over the 6 month follow-up period.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HL081028-05
Application #
7929552
Study Section
Special Emphasis Panel (ZHL1)
Project Start
Project End
2012-08-31
Budget Start
2009-09-01
Budget End
2012-08-31
Support Year
5
Fiscal Year
2009
Total Cost
$600,060
Indirect Cost

  Institution

Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048

  Publications

Ramireddy, Archana; Brodt, Chad R; Mendizabal, Adam M et al. (2017) Effects of Transendocardial Stem Cell Injection on Ventricular Proarrhythmia in Patients with Ischemic Cardiomyopathy: Results from the POSEIDON and TAC-HFT Trials. Stem Cells Transl Med 6:1366-1372
Golpanian, Samuel; El-Khorazaty, Jill; Mendizabal, Adam et al. (2015) Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy patients. J Am Coll Cardiol 65:125-32
Yoneyama, Kihei; Lima, João A C (2015) Alcohol consumption and myocardial remodeling in elderly women and men. Circ Cardiovasc Imaging 8:
Magalhães, Tiago A; Kishi, Satoru; George, Richard T et al. (2015) Combined coronary angiography and myocardial perfusion by computed tomography in the identification of flow-limiting stenosis - The CORE320 study: An integrated analysis of CT coronary angiography and myocardial perfusion. J Cardiovasc Comput Tomogr 9:438-45
Heldman, Alan W; DiFede, Darcy L; Fishman, Joel E et al. (2014) Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA 311:62-73
Suncion, Viky Y; Ghersin, Eduard; Fishman, Joel E et al. (2014) Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?: An analysis from the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial. Circ Res 114:1292-301
Karantalis, Vasileios; DiFede, Darcy L; Gerstenblith, Gary et al. (2014) Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Ce Circ Res 114:1302-10
Donekal, Sirisha; Venkatesh, Bharath A; Liu, Yuan Chang et al. (2014) Interstitial fibrosis, left ventricular remodeling, and myocardial mechanical behavior in a population-based multiethnic cohort: the Multi-Ethnic Study of Atherosclerosis (MESA) study. Circ Cardiovasc Imaging 7:292-302
Malliaras, Konstantinos; Makkar, Raj R; Smith, Rachel R et al. (2014) Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction). J Am Coll Cardiol 63:110-22
Williams, Adam R; Hatzistergos, Konstantinos E; Addicott, Benjamin et al. (2013) Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation 127:213-23

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