A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration
| Autor: | Louis Vincent, Vasileios Karantalis, Kevin Collon, Raul Mitrani, Samuel Golpanian, Bryon A. Tompkins, Ana Marie Landin, Ariel Wolf, Monisha N. Banerjee, Cristina Sanina, Wayne Balkan, Alan W. Heldman, Makoto Natsumeda, Victoria Florea, Kostas E. Hatzistergos, Julia Fritsch, Nilesh D. Kashikar, Ivonne Hernandez Schulman, Angela C. Rieger, Viky Y. Loescher, Jose Rodriguez, Luiza Bagno, Muzammil Mushtaq, Marcos Rosado, Anthony J. Kanelidis, Joshua M. Hare |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cardiac function curve medicine.medical_specialty Combination therapy Swine Heart Ventricles Myocardial Ischemia Magnetic Resonance Imaging Cine 030204 cardiovascular system & hematology Mesenchymal Stem Cell Transplantation Injections 03 medical and health sciences 0302 clinical medicine Immune system Internal medicine Animals Transplantation Homologous Medicine IL-2 receptor Ischemic cardiomyopathy Ventricular Remodeling business.industry Myocardium Mesenchymal stem cell FOXP3 Mesenchymal Stem Cells Disease Models Animal 030104 developmental biology Immunology Cardiology Female Stem cell Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of the American College of Cardiology. 70:2504-2515 |
| ISSN: | 0735-1097 |
| Popis: | Background The combination of autologous mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) synergistically reduces scar size and improves cardiac function in ischemic cardiomyopathy. Whereas allogeneic (allo-)MSCs are immunoevasive, the capacity of CSCs to similarly elude the immune system remains controversial, potentially limiting the success of allogeneic cell combination therapy (ACCT). Objectives This study sought to test the hypothesis that ACCT synergistically promotes cardiac regeneration without provoking immunologic reactions. Methods Gottingen swine with experimental ischemic cardiomyopathy were randomized to receive transendocardial injections of allo-MSCs + allo-CSCs (ACCT: 200 million MSCs/1 million CSCs, n = 7), 200 million allo-MSCs (n = 8), 1 million allo-CSCs (n = 4), or placebo (Plasma-Lyte A, n = 6). Swine were assessed by cardiac magnetic resonance imaging and pressure volume catheterization. Immune response was tested by histologic analyses. Results Both ACCT and allo-MSCs reduced scar size by −11.1 ± 4.8% (p = 0.012) and −9.5 ± 4.8% (p = 0.047), respectively. Only ACCT, but not MSCs or CSCs, prevented ongoing negative remodeling by offsetting increases in chamber volumes. Importantly, ACCT exerted the greatest effect on systolic function, improving the end-systolic pressure-volume relation (+0.98 ± 0.41 mm Hg/ml; p = 0.016). The ACCT group had more phospho-histone H3+ (a marker of mitosis) cardiomyocytes (p = 0.04), and noncardiomyocytes (p = 0.0002) than did the placebo group in some regions of the heart. Inflammatory sites in ACCT and MSC-treated swine contained immunotolerant CD3+/CD25+/FoxP3+ regulatory T cells (p Conclusions ACCT demonstrates synergistic effects to enhance cardiac regeneration and left ventricular functional recovery in a swine model of chronic ischemic cardiomyopathy without adverse immunologic reaction. Clinical translation to humans is warranted. |
| Databáze: | OpenAIRE |
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