PLoS ONE (Jan 2011)

Histone deacetylase inhibition enhances self renewal and cardioprotection by human cord blood-derived CD34 cells.

  • Ilaria Burba,
  • Gualtiero I Colombo,
  • Lidia Irene Staszewsky,
  • Marco De Simone,
  • Paolo Devanna,
  • Simona Nanni,
  • Daniele Avitabile,
  • Fabiola Molla,
  • Simona Cosentino,
  • Ilaria Russo,
  • Noeleen De Angelis,
  • Annarita Soldo,
  • Antonella Biondi,
  • Elisa Gambini,
  • Carlo Gaetano,
  • Antonella Farsetti,
  • Giulio Pompilio,
  • Roberto Latini,
  • Maurizio C Capogrossi,
  • Maurizio Pesce

DOI
https://doi.org/10.1371/journal.pone.0022158
Journal volume & issue
Vol. 6, no. 7
p. e22158

Abstract

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BACKGROUND: Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs), have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of "enhancement" strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit. PRINCIPAL FINDINGS: Pharmacologic inhibition of histone deacetylases (HDACs) is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34(+) were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction. CONCLUSIONS: Our results show that HDAC blockade leads to phenotype changes in CD34(+) cells with enhanced self renewal and cardioprotection.