Abstract 13363: Fate Mapping of CXCR4+ Cells in the Ischemic Heart Utilizing a Novel CXCR4 (BAC)-EGFP Transgenic Mouse Model
Objective: Data from our lab suggest that stabilization of the cardiac SDF-1/CXCR4 axis preserves myocardial function and attenuates ischemic cardiomyopathy. However, the basic mechanisms of SDF-1/CXCR4 mediated repair remains barely understood. Here, we aimed to fate-map CXCR4+ cell populations in the bone marrow (BM), peripheral blood (PB) and the heart utilizing novel CXCR4(BAC)-EGFP reporter mice. Methods: To track the fate of CXCR4+ cells, genetically tagged CXCR4-EGFP BAC reporter mice carrying an EGFP sequence downstream of the translational (ATG) start side of a 200kb bacterial artificial chromosome (BAC) were utilized. FACS and immunhistochemical analyses of CXCR4-EGFP+ BM, PB and heart cells were analyzed under normoxaemic and ischemic conditions.
Results: FACS of transgenic CXCR4-EGFP BM revealed that CXCR4+ was most frequently expressed on CD11b+ monocytes, angiogenic CD31+ , CD34+, c-kit+ , and Flk1+ cells, as well as stem cell populations like ACC133+ and Lin-/c-kit+/Sca-1+. After ischemia CXCR4+/CD11b+ monocytes and CXCR4+/Flk+ cells were upregulated. In the PB the most frequent cell populations were CXCR4+/CD31+ and CXCR4+/Sca-1+. In the ischemic heart, CXCR4 was predominantly expressed on CD11b+ monocytes, suggesting an important role in post ischemic remodeling. CXCR4 was expressed to a less amount on migrating angiogenic CD31+ , CD34+, c-kit+, and Flk1+ cells, as well as stem cell populations like ACC133+, and Lin-/c-kit+/Sca-1+ cells. Staining of CXCR4-EGFP+ cells with PEACAM (CD31) revealed significant co-expression of a subpopulation of CXCR4+ cells in capillaries after ischemia (Fig. 1). In conclusion, our data show that CXCR4 is highly expressed on angiogenic and on stem cell populations in the BM, PB and the myocardium. In the ischemic heart, CXCR4-EGFP+ target to vascular structures and predominantly to angiogenic CXCR4+/CD11b+ cells.
- © 2012 by American Heart Association, Inc.