Intramyocardial Stem Cell Injection in Patients With Ischemic Cardiomyopathy Functional Recovery and Reverse Remodeling

Interdisciplinary Stem Cell Institute, Department of Medicine, University of Miami Miller School of Medicine, 1501 NW 10th Ave., Miami, FL 33136, USA.
Circulation Research (Impact Factor: 11.02). 03/2011; 108(7):792-6. DOI: 10.1161/CIRCRESAHA.111.242610
Source: PubMed


Transcatheter, intramyocardial injections of bone marrow-derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy.
We used cardiac MRI (CMR) in patients with left ventricular (LV) dysfunction related to remote myocardial infarction (MI) to test the hypothesis that bone marrow progenitor cell injection causes functional recovery of scarred myocardium and reverse remodeling.
Eight patients (aged 57.2±13.3 years) received transendocardial, intramyocardial injection of autologous bone marrow progenitor cells (mononuclear or mesenchymal stem cells) in LV scar and border zone. All patients tolerated the procedure with no serious adverse events. CMR at 1 year demonstrated a decrease in end diastolic volume (208.7±20.4 versus 167.4±7.32 mL; P=0.03), a trend toward decreased end systolic volume (142.4±16.5 versus 107.6±7.4 mL; P=0.06), decreased infarct size (P<0.05), and improved regional LV function by peak Eulerian circumferential strain in the treated infarct zone (-8.1±1.0 versus -11.4±1.3; P=0.04). Improvements in regional function were evident at 3 months, whereas the changes in chamber dimensions were not significant until 6 months. Improved regional function in the infarct zone strongly correlated with reduction of end diastolic volume (r(2)=0.69, P=0.04) and end systolic volume (r(2)=0.83, P=0.01).
These data suggest that transcatheter, intramyocardial injections of autologous bone marrow progenitor cells improve regional contractility of a chronic myocardial scar, and these changes predict subsequent reverse remodeling. The findings support the potential clinical benefits of this new treatment strategy and ongoing randomized clinical trials.

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Available from: Alan Heldman, Aug 04, 2014
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    • "Interestingly, further analysis of imaging data found that the functional effects of MSCs appeared preferentially at local sites of MSC injection whilst scar reduction was seen more globally (Suncion et al. 2014). Similar effects of MSCs on scar were seen by Williams et al. who used percutaneous transendocardial injections (Williams et al. 2011). The Transendocardial Autologous Cells in Ischemic Heart Failure Trial (TAC-HFT) also used percutaneous intramycoardial injections to compare efficacy of MSCs to BMMNCs (Heldman et al. 2014). "
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    ABSTRACT: Following significant injury, the heart undergoes induced compensation and gradually deteriorates towards impending heart failure. Current therapy slows but does not halt the resultant adverse remodeling. Stem cell therapy, however, has the potential to regenerate or repair infarcted heart tissue and therefore is a promising therapeutic strategy undergoing intensive investigation. Due to the wide range of stem cells investigated, it is difficult to navigate this field. This review aims to summarize the main types of stem cells (both of cardiac and extra-cardiac origin) that possess promising therapeutic potential. Particular focus is placed on clinical trials supporting this therapeutic strategy.
    Full-text · Article · Aug 2014 · SpringerPlus
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    • "In translational research, stem cell study is one of the most actively proceeding field. With the help of these preclinical research efforts, at present, new and exciting stem cell therapies are already being applied in clinical applications, as seen in the SCIPIO, Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS), the PercutaneOus StEm Cell Injection Delivery Effects on Neomyogenesis pilot study (POSEIDON), dilated cardiomyopathy (POSEIDON-DCM), and Transendocardial Autologous Cells in Ischemic Heart Failure Trial (TACHFT) trials.10)38-41) "
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    ABSTRACT: Animal models have long been developed for cardiovascular research. These animal models have been helpful in understanding disease, discovering potential therapeutics, and predicting efficacy. Despite many efforts, however, translational study has been underestimated. Recently, investigations have identified stem cell treatment as a potentially promising cell therapy for regenerative medicine, largely because of the stem cell's ability to differentiate into many functional cell types. Stem cells promise a new era of cell-based therapy for salvaging the heart. However, stem cells have the potential risk of tumor formation. These properties of stem cells are considered a major concern over the efficacy of cell therapy. The translational/preclinical study of stem cells is essential but only at the beginning stages. What types of heart disease are indicated for stem cell therapy, what type of stem cell, what type of animal model, how do we deliver stem cells, and how do we improve heart function? These may be the key issues that the settlement of which would facilitate the transition of stem cell research from bench to bedside. In this review article, we discuss state-of-the-art technology in stem cell therapies for cardiovascular diseases.
    Full-text · Article · Aug 2013 · Korean Circulation Journal
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    • "Cell‐based therapy is emerging as a potentially transformative treatment for advanced heart failure. Many cell types isolated from either a bone marrow or cardiac biopsy are currently under investigation in clinical trials.7–9 Mesenchymal stem cells (MSCs) were first isolated in the 1970s and are a highly attractive cell therapy for heart failure. "
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    ABSTRACT: Background Intramyocardial injection of mesenchymal stem cells (MSCs) in chronic ischemic cardiomyopathy is associated with reverse remodeling in experimental models and humans. Here, we tested the hypothesis that allogeneic MSC therapy drives ventricular remodeling by producing durable and progressive scar size reduction in ischemic cardiomyopathy. Methods and Results Gottingen swine (n=12) underwent left anterior descending coronary artery myocardial infarction (MI), and 3 months post‐MI animals received either intramyocardial allogeneic MSC injection (200 mol/L cells; n=6) or left ventricle (LV) catheterization without injection (n=6). Swine were followed with serial cardiac magnetic resonance imaging for 9 months to assess structural and functional changes of the LV. Intramyocardial injection was performed using an integrated imaging platform combining electroanatomical mapping unipolar voltage and 3‐dimensional cardiac magnetic resonance imaging angiography–derived anatomy to accurately target infarct border zone injections. MSC‐treated animals had a 19.62±2.86% reduction in scar size at 3 months postinjection, which progressed to 28.09±2.31% from 3 to 6 months postinjection (P<0.0001). MSC‐treated animals had unchanged end‐diastolic volume (EDV; P=0.08) and end‐systolic volume (ESV; P=0.28) from preinjection to 6 months postinjection, whereas controls had progressive dilatation in both EDV (P=0.0002) and ESV (P=0.0002). In addition, MSC‐treated animals had improved LV sphericity index. Percentage change in infarct size correlated with percentage change in EDV (r=0.68; P=0.01) and ESV (r=0.77; P=0.001). Ejection fraction increased from 29.69±1.68% to 35.85±2.74% at 3 months post‐MSC injection and progressed to 39.02±2.42% 6 months postinjection (P=0.0001), whereas controls had a persistently depressed ejection fraction during follow‐up (P=0.33). Conclusion Intramyocardial injection of allogeneic MSCs leads to a sustained and progressive reduction in infarct size, which in turn drives reverse remodeling and increases in ejection fraction. These findings support ongoing biological activity of cell therapy for substantial periods and suggest optimal end points for future clinical trials.
    Full-text · Article · Apr 2013 · Journal of the American Heart Association
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