Publications (2)14.74 Total impact
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ABSTRACT: Over the past decade the cardiovascular regenerative medicine field has made significant advances in our understanding and treatment of injured myocardium. Prior to stem cell therapy, available treatments for cardiovascular disease were unable to repair or regenerate the damaged heart. Stem cell therapy is increasingly becoming a viable option to prevent and treat cardiac dysfunction. A number of exogenous stem cell populations have been examined for their ability to participate in cardiac repair. Their application in the clinical setting will be reviewed here. The molecular pathways that work in concert to orchestrate a systemic endogenous stem cell response to cardiac injury have also begun to be defined. A potential strategy for future therapeutics is the manipulation of these endogenous pathways via pharmacological or biopharmaceutical approaches. In this review we begin to formulate the discussion that the best future therapeutic option to regenerate end organ function will be a combination of programmed stem cells and biopharmaceuticals that modulate regenerative signaling to bolster the natural in vivo cellular and signaling mechanisms.Frontiers in bioscience (Elite edition) 01/2013; E5:232-248.
Article: Myocardial CXCR4 expression is required for mesenchymal stem cell mediated repair following acute myocardial infarction.[show abstract] [hide abstract]
ABSTRACT: Overexpression of stromal cell-derived factor-1 in injured tissue leads to improved end-organ function. In this study, we quantify the local trophic effects of mesenchymal stem cell (MSC) stromal cell-derived factor-1 release on the effects of MSC engraftment in the myocardium after acute myocardial infarction. Conditional cardiac myocyte CXCR4 (CM-CXCR4) null mice were generated by use of tamoxifen-inducible cardiac-specific cre by crossing CXCR4 floxed with MCM-cre mouse. Studies were performed in littermates with (CM-CXCR4 null) or without (control) tamoxifen injection 3 weeks before acute myocardial infarction. One day after acute myocardial infarction, mice received 100,000 MSC or saline via tail vein. We show α-myosin heavy chain MerCreMer and the MLC-2v promoters are active in cardiac progenitor cells. MSC engraftment in wild-type mice decreased terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling positive CM (-44%, P<0.01), increased cardiac progenitor cell recruitment (100.9%, P<0.01), and increased cardiac myosin-positive area (39%, P<0.05) at 4, 7, and 21 days after acute myocardial infarction, respectively. MSC in wild-type mice resulted in 107.4% (P<0.05) increase in ejection fraction in comparison with 25.9% (P=NS) increase in CM-CXCR4 null mice. These differences occurred despite equivalent increases (16%) in vascular density in response to MSC infusion in wild-type and CM-CXCR4 null mice. These data demonstrate that the local trophic effects of MSC require cardiac progenitor cell and CM-CXCR4 expression and are mediated by MSC stromal cell-derived factor-1 secretion. Our results further demonstrate and quantify for the first time a specific paracrine mechanism of MSC engraftment. In the absence of CM-CXCR4 expression, there is a significant loss of functional benefit in MSC-mediated repair despite equal increases in vascular density.Circulation 06/2012; 126(3):314-24. · 14.74 Impact Factor