Beschreibung:
<jats:sec>
<jats:title>Background—</jats:title>
<jats:p>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.</jats:p>
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<jats:title>Methods and Results—</jats:title>
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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%,
<jats:italic>P</jats:italic>
<0.01), increased cardiac progenitor cell recruitment (100.9%,
<jats:italic>P</jats:italic>
<0.01), and increased cardiac myosin-positive area (39%,
<jats:italic>P</jats:italic>
<0.05) at 4, 7, and 21 days after acute myocardial infarction, respectively. MSC in wild-type mice resulted in 107.4% (
<jats:italic>P</jats:italic>
<0.05) increase in ejection fraction in comparison with 25.9% (
<jats:italic>P</jats:italic>
=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.
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<jats:title>Conclusions—</jats:title>
<jats:p>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.</jats:p>
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