201. Human cardiac mesoangioblasts isolated from hypertrophic cardiomyopathies are greatly reduced in proliferation and differentiation potency.
- Author
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Gálvez BG, Covarello D, Tolorenzi R, Brunelli S, Dellavalle A, Crippa S, Mohammed SA, Scialla L, Cuccovillo I, Molla F, Staszewsky L, Maisano F, Sampaolesi M, Latini R, and Cossu G
- Subjects
- Adult Stem Cells transplantation, Animals, Aortic Valve Insufficiency pathology, Cell Differentiation, Cell Proliferation, Cell Separation, Cells, Cultured, Chick Embryo, Humans, Hypertrophy, Left Ventricular pathology, Mice, Mice, Inbred C57BL, Mice, SCID, Mitral Valve Insufficiency pathology, Myocardial Infarction pathology, Myocardial Infarction therapy, Myocytes, Cardiac pathology, Rats, Stem Cell Transplantation, Adult Stem Cells pathology, Cardiomyopathy, Hypertrophic pathology, Myocardium pathology
- Abstract
Aims: Our objective was to test whether progenitor cell proliferation and differentiation potential may vary depending upon the disease of the donor., Methods and Results: Human cardiac mesoangioblasts were isolated from cardiac muscle biopsies of patients undergoing open heart surgery for correction of mitral regurgitation following an acute myocardial infarction (MR-MI) or correction of mitral and aortic regurgitation with ensuing left ventricular hypertrophy (MAR-LVH). The cells express surface markers and cardiac genes similar to mouse cardiac mesoangioblasts; they have limited self-renewing and clonogenic activity and are committed mainly to cardiogenesis. Although cardiac differentiation can be induced by 5-azacytidine or by co-culture with rat neonatal cardiomyocytes, human cells do not contract spontaneously like their mouse counterparts. When locally injected in the infarcted myocardium of immunodeficient mice, cardiac mesoangioblasts generate a chimeric heart that contains human myocytes and some capillaries; likewise, they colonize chick embryo hearts when transplanted in ovo. At variance with cells from patients with MR-MI, when isolation was performed on biopsies from MAR-LVH, cells could be isolated in much lower numbers, proliferated less extensively and failed to differentiate., Conclusion: Cardiac mesoangioblasts are present in the human heart but this endogenous progenitor population is progressively exhausted, possibly by continuous and inefficient regeneration attempts.
- Published
- 2009
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