title: Histone deacetylase inhibition enhances self renewal and cardioprotection by human cord blood-derived CD34 cells.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Burba
authors.forename: Gualtiero I
authors.initials: GI
authors.lastname: Colombo
authors.forename: Lidia Irene
authors.initials: LI
authors.lastname: Staszewsky
authors.forename: Marco
authors.initials: M
authors.lastname: De Simone
authors.forename: Paolo
authors.initials: P
authors.lastname: Devanna
authors.forename: Simona
authors.initials: S
authors.lastname: Nanni
authors.forename: Daniele
authors.initials: D
authors.lastname: Avitabile
authors.forename: Fabiola
authors.initials: F
authors.lastname: Molla
authors.forename: Simona
authors.initials: S
authors.lastname: Cosentino
authors.forename: Ilaria
authors.initials: I
authors.lastname: Russo
authors.forename: Noeleen
authors.initials: N
authors.lastname: De Angelis
authors.forename: Annarita
authors.initials: A
authors.lastname: Soldo
authors.forename: Antonella
authors.initials: A
authors.lastname: Biondi
authors.forename: Elisa
authors.initials: E
authors.lastname: Gambini
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaetano
authors.forename: Antonella
authors.initials: A
authors.lastname: Farsetti
authors.forename: Giulio
authors.initials: G
authors.lastname: Pompilio
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pesce
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D016000:Cluster Analysis; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010641:Phenotype; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D002316:Cardiotonic Agents; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D006655:Histone Deacetylases