Human cardiac mesoangioblasts isolated from hypertrophic cardiomyopathies are greatly reduced in proliferation and differentiation potency
Gálvez, Beatriz G × Covarello, Diego Tolorenzi, Rosanna Brunelli, Silvia Dellavalle, Arianna Crippa, Stefania Mohammed, Salman Afroze Azmi Scialla, Ludovica Cuccovillo, Ivan Molla, Fabiola Staszewsky, Lidia Maisano, Francesco Sampaolesi, Maurilio Latini, Roberto Cossu, Giulio #
British Medical Association
Cardiovascular Research vol:83 issue:4 pages:707-716
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.