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Ex vivo acidic preconditioning enhances bone marrow ckit+ cell therapeutic potential via increased CXCR4 expression.
MedLine Citation:
PMID:  21784762     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aims The chemokine receptor CXCR4 modulates endothelial progenitor cell migration, homing, and differentiation, and plays a key role in cardiovascular regeneration. Here we examined the effect of ex vivo acidic preconditioning (AP) on CXCR4 expression and on the regenerative potential of mouse bone marrow (BM) ckit(+) cells. Methods and results Acidic preconditioning was achieved by exposing BM ckit(+) cells to hypercarbic acidosis (pH 7.0) for 24 h; control cells were kept at pH 7.4. Acidic preconditioning enhanced CXCR4 and stromal cell-derived factor 1 (SDF-1) mRNA levels, as well as CXCR4 phosphorylation. Acidic preconditioning ability to modulate CXCR4 expression depended on cytosolic calcium [Ca(2+)](i) mobilization and on nitric oxide (NO), as determined by [Ca(2+)](i) buffering with BAPTA, and by treatment with the NO donor (DETA/NO) and the NO synthase inhibitor (L-NAME). Further, AP increased SDF-1-driven chemotaxis, transendothelial migration, and differentiation toward the endothelial lineage in vitro. In a mouse model of hindlimb ischaemia, control and AP ckit(+) cells were transplanted into the ischaemic muscle; AP cells accelerated blood flow recovery, increased capillary, and arteriole number as well as the number of regenerating muscle fibres vs. control. These effects were abolished by treating AP cells with L-NAME. Conclusion Acidic preconditioning represents a novel strategy to enhance BM ckit(+) cell therapeutic potential via NO-dependent increase in CXCR4 expression.
Authors:
Chiara Cencioni; Roberta Melchionna; Stefania Straino; Marta Romani; Claudia Cappuzzello; Valentina Annese; Joseph C Wu; Giulio Pompilio; Angela Santoni; Carlo Gaetano; Monica Napolitano; Maurizio C Capogrossi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-22
Journal Detail:
Title:  European heart journal     Volume:  -     ISSN:  1522-9645     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratorio di Biologia vascolare e Medicina Rigenerativa, Centro Cardiologico Monzino-IRCCS, Milan, Italy.
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