Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction

Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability “in vitro” and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjure...

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Bibliographic Details
Published in:Circulation Research 2004-10, Vol.95 (7), p.742-748
Main Authors: Fernández-Avilés, Francisco, San Román, José Alberto, García-Frade, Javier, Fernández, María Eugenia, Peñarrubia, María Jesús, de la Fuente, Luis, Gómez-Bueno, Manuel, Cantalapiedra, Alberto, Fernández, Jesús, Gutierrez, Oliver, Sánchez, Pedro L, Hernández, Carolina, Sanz, Ricardo, García-Sancho, Javier, Sánchez, Ana
Format: Article
Language:English
Subjects:
Aged
Animals
Biological and medical sciences
Bone Marrow Cells - physiology
Cardiac Catheterization
Cardiology. Vascular system
Cell Differentiation
Cold Temperature - adverse effects
Combined Modality Therapy
Connexin 43 - biosynthesis
Connexin 43 - genetics
Coronary heart disease
Coronary Restenosis - prevention & control
Echocardiography, Stress
Female
Fibrinolytic Agents - therapeutic use
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Heart
Heart - physiology
Humans
Magnetic Resonance Imaging
Male
Medical sciences
Mice
Mice, Inbred BALB C
Middle Aged
Myocardial Infarction - drug therapy
Myocardial Infarction - pathology
Myocardial Infarction - therapy
Myocardial Reperfusion
Myocarditis. Cardiomyopathies
Myocytes, Cardiac - cytology
Organ Culture Techniques
Regeneration
Stem Cell Transplantation
Stents
Stroke Volume
Thrombolytic Therapy
Tissue Plasminogen Activator - therapeutic use
Transplantation, Autologous
Ventricular Remodeling - physiology
Vertebrates: cardiovascular system
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Summary:Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability “in vitro” and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78±41×10 per patient) were intracoronarily transplanted 13.5±5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11±5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.
ISSN:0009-7330
1524-4571
1524-4539
DOI:10.1161/01.RES.0000144798.54040.ed