This Specialized Center for Cell Therapeutics proposal aims to develop cellular cardiomyoplasty for the treatment of ischemic heart disease, both post-myocardial infarction left ventricular dysfunction as well as chronic ischemic cardiomyopathy. Currently, there is extraordinary enthusiasm for the development of cell-based therapies for diseases resulting from ischemic damage to the myocardium. Rapid advances have been made in animal models and preliminary clinical trials suggest that cardiac function in acute and chronic heart disease may be improved. Currently the bone marrow remains as a highly promising source of precursor cells for cardiac repair. Our group has been involved in collaboration with Osiris Therapeutics in developing bone-marrow derived mesenchymal stem cells (MSCs) for the use of cellular cardiomyoplasty, and the results of this work have led to the upcoming initiation of the first clinical trial of this cell type for humans with myocardial infarction. In addition, cardiac stem cells have now been identified that can be amplified in culture as a source of cells for cardiac repair. This proposal is based upon extensive basic and preclinical data supporting the value of both MSCs and cardiac stem cells (CSCs) for cellular cardiomyoplasty. A major strength of the approach is our ability to prepare adequate numbers of cardiac stem cells from biopsy specimens for use in therapeutic applications. The approach is three-fold with substantial synergies. First, in Project 1 MSCs will be explored in clinical trials of humans with ischemic cardiomyopathy based on an existing extensive pre-clinical database, an established safety record in humans, and already-planned clinical trials for patients with acute myocardial infarction. Second, we will concurrently in Project 2 continue characterizing CSCs obtained from humans and perform relevant preclinical experiments. Finally, based on the substantial experience obtained in Project 1 with delivery techniques and efficacy monitoring developed, and the cellular methods perfected in Project 2, we will perform clinical trials of CSCs in Project 3. Together, this program will have the capability of performing highly-relevant and clinically informative trials that will be guided and refined by the latest advances in basic cell biology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HL081028-02
Application #
7312644
Study Section
Special Emphasis Panel (ZHL1)
Project Start
Project End
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$1,181,793
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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
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
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:
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

Showing the most recent 10 out of 71 publications