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

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 eff...

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Published in:PloS one 2011, Vol.6 (7), p.e22158-e22158
Main Authors: Burba, Ilaria, Colombo, Gualtiero I, Staszewsky, Lidia Irene, De Simone, Marco, Devanna, Paolo, Nanni, Simona, Avitabile, Daniele, Molla, Fabiola, Cosentino, Simona, Russo, Ilaria, De Angelis, Noeleen, Soldo, Annarita, Biondi, Antonella, Gambini, Elisa, Gaetano, Carlo, Farsetti, Antonella, Pompilio, Giulio, Latini, Roberto, Capogrossi, Maurizio C, Pesce, Maurizio
Format: Article
Language:English
Subjects:
Acetylation - drug effects
Angiogenesis
Animals
Antigens, CD34 - metabolism
Biology
Biomarkers - metabolism
Blood
Bone marrow
Cardiomyopathy
Cardiotonic Agents - pharmacology
CD34 antigen
Cell adhesion & migration
Cell Proliferation - drug effects
Cell self-renewal
Clone Cells
Cluster Analysis
Conditioning
Cord blood
Drug dosages
Epigenetics
Fetal Blood - cytology
Fibroblasts
Flow Cytometry
Gene expression
Gene Expression Profiling
Growth factors
Heart
Heart attacks
Heart diseases
Histone deacetylase
Histone Deacetylase Inhibitors - pharmacology
Histone Deacetylases - metabolism
Humans
Immune system
Immunodeficiency
Inhibition
Ischemia
Medicine
Mice
Myocardial infarction
Myocardium
Osteoprogenitor cells
Peripheral blood
Pharmacology
Phenotype
Prostate cancer
Regeneration - drug effects
Risk analysis
Risk factors
Rodents
Stem cell transplantation
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Tissues
Valproic acid
Valproic Acid - pharmacology
Vascularization
Wound Healing - drug effects
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Summary: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. 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. Our results show that HDAC blockade leads to phenotype changes in CD34(+) cells with enhanced self renewal and cardioprotection.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0022158