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Ex vivo acidic preconditioning enhances bone marrow ckit+ cell therapeutic potential via increased CXCR4 expression.
- Source :
-
European heart journal [Eur Heart J] 2013 Jul; Vol. 34 (26), pp. 2007-16. Date of Electronic Publication: 2011 Jul 22. - Publication Year :
- 2013
-
Abstract
- 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.<br />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.<br />Conclusion: Acidic preconditioning represents a novel strategy to enhance BM ckit(+) cell therapeutic potential via NO-dependent increase in CXCR4 expression.
- Subjects :
- Animals
Bone Marrow Cells cytology
Cell Differentiation physiology
Cell Proliferation
Chelating Agents pharmacology
Chemokine CXCL12 metabolism
Egtazic Acid analogs & derivatives
Egtazic Acid pharmacology
Endothelial Cells cytology
Endothelial Cells physiology
Hindlimb blood supply
Hydrogen-Ion Concentration
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Ischemia prevention & control
Ischemic Preconditioning methods
Male
Mice
Nitric Oxide Donors metabolism
Bone Marrow Cells physiology
Bone Marrow Transplantation methods
Proto-Oncogene Proteins c-kit metabolism
Receptors, CXCR4 metabolism
Regeneration physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-9645
- Volume :
- 34
- Issue :
- 26
- Database :
- MEDLINE
- Journal :
- European heart journal
- Publication Type :
- Academic Journal
- Accession number :
- 21784762
- Full Text :
- https://doi.org/10.1093/eurheartj/ehr219