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

Beatriz G. Gálvez, Diego Covarello, Rosanna Tolorenzi, Silvia Brunelli, Arianna Dellavalle, Stefania Crippa, Salman Afroze Azmi Mohammed, Ludovica Scialla, Ivan Cuccovillo, Fabiola Molla, Lidia Staszewsky, Francesco Maisano, Maurilio Sampaolesi, Roberto Latini, Giulio Cossu

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)707-716
Number of pages10
JournalCardiovascular Research
Volume83
Issue number4
DOIs
Publication statusPublished - Sep 2009

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Keywords

  • Hypertrophy
  • Mesoangioblasts
  • Mitral regurgitation
  • Regeneration

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Gálvez, B. G., Covarello, D., Tolorenzi, R., Brunelli, S., Dellavalle, A., Crippa, S., Mohammed, S. A. A., Scialla, L., Cuccovillo, I., Molla, F., Staszewsky, L., Maisano, F., Sampaolesi, M., Latini, R., & Cossu, G. (2009). Human cardiac mesoangioblasts isolated from hypertrophic cardiomyopathies are greatly reduced in proliferation and differentiation potency. Cardiovascular Research, 83(4), 707-716. https://doi.org/10.1093/cvr/cvp159