| Ex vivo acidic preconditioning enhances bone marrow ckit+ cell therapeutic potential via increased CXCR4 expression. | |
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MedLine Citation:
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PMID: 21784762 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2011-7-22 |
Journal Detail:
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Title: European heart journal Volume: - ISSN: 1522-9645 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8006263 Medline TA: Eur Heart J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Laboratorio di Biologia vascolare e Medicina Rigenerativa, Centro Cardiologico Monzino-IRCCS, Milan, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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