Circulation Research. 2004;95:742-748
Published online before print September 9, 2004, doi: 10.1161/01.RES.0000144798.54040.ed
Published online before print September 9, 2004, doi: 10.1161/01.RES.0000144798.54040.ed
© 2004 American Heart Association, Inc.
Clinical Research |
Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction
From the Instituto de Ciencias del Corazón (ICICOR) (F.F.-A., J.A.S.R., L.d.l.F., M.G.-B., P.L.S., C.H., R.S.), Hospital Clínico-Universitario, Servicio de Hematología (J.G.-F., M.J.P., A.C., O.G.), Hospital Universitario del Río Hortega, and Instituto de Biología y Genética Molecular (M.E.F., J.F., J.G.-S., A.S.), Facultad de Medicina, Universidad de Valladolid y CSIC, Valladolid, Spain.
Correspondence to Francisco Fernández-Avilés, ICICOR, Hospital Clínico Universitario. C/O Ramón y Cajal 3, E-47005-Valladolid, Spain. E-mail faviles{at}secardiologia.es
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±41x106 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.
Key Words: myocardial infarction • restenosis • myogenesis • cardiomyocytes • autologous cell transplantation • remodeling • bone marrow • connexin43
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