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Cardiovascular Research Advance Access [Accepted Manuscript] published online on May 20, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp159
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Human cardiac mesoangioblasts isolated from hypertrophic cardiomyopathies are greatly reduced in proliferation and differentiation potency

Beatriz G. Gálvez1, Diego Covarello1, Rosanna Tolorenzi1, Silvia Brunelli1,2, Arianna Dellavalle1, Stefania Crippa3, Mohammed Salman4, Ludovica Scialla4, Ivan Cuccovillo5, Fabiola Molla5, Lidia Staszewsky5, Francesco Maisano6, Maurilio Sampaolesi3, Roberto Latini5 and Giulio Cossu1,7

1 Division of Regenerative Medicine, San Raffaele Scientific Institute, Milan, Italy
2 Dept. of Experimental Medicine, University of Milano-Bicocca, Italy
3 Stem Cell Research Institut, University Hospital Gasthuisberg, Leuven, Belgium
4 Cardiology, Faculty of Medicine, University "La Sapienza" Rome, Italy
5 Dept. of Cardiovascular Research, Mario Negri Institute, Milan, Italy
6 Dept. of Cardiovascular Surgery. San Raffaele Scientific Institute, Milan, Italy
7 Dept. of Biology, University of Milan, Italy

Corresponding author: Beatriz G. Gálvez, PhD Division of Regenerative Medicine, San Raffaele Scientific Institute, 58 Via Olgettina, 20132 Milan, Italy. Phone: +390226434954; Fax: +390226434621. E-mail: bggalvez{at}hotmail.com

Aims: Our objective was to test whether progenitor cell proliferation and differentiation potential may vary depending upon the disease of the donor.

Methods: 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).

Results: 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.

Conclusions: Cardiac mesoangioblasts are present in the human heart but this endogenous progenitor population is progressively exhausted, possibly by continuous and inefficient regeneration attempts.

KEYWORDS regeneration; mitral regurgitation; hypertrophy; mesoangioblasts

Time for primary review: 24 Days


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