Comparative effects of mesenchymal progenitor cells, endothelial progenitor cells, or their combination on myocardial infarct regeneration and cardiac.

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Comparative effects of mesenchymal progenitor cells, endothelial progenitor cells, or their combination on myocardial infarct regeneration and cardiac function Erik J. Suuronen, PhD, Joel Price, MD, John P. Veinot, MD, Kathryn Ascah, MD, Varun Kapila, MD, Xue-Wei Guo, MD, PhD, Serena Wong, MSc, Thierry G. Mesana, MD, PhD, Marc Ruel, MD, MPH The Journal of Thoracic and Cardiovascular Surgery Volume 134, Issue 5, Pages 1249-1258 (November 2007) DOI: 10.1016/j.jtcvs.2007.07.028 Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Experimental design. A, The left descending coronary artery was ligated. B, Echocardiographic analysis was performed 14 days after ligation. C, At post–myocardial infarction day 21, cell transplantation was performed into the infarcted region. D, Echocardiography was performed 1 month after cell transplantation, and the experiment was terminated. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1249-1258DOI: (10.1016/j.jtcvs.2007.07.028) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Cell engraftment and differentiation. Representative images of the following are shown: A, 4′,6-diamidino-2′-phenylindole (DAPI)–labeled nuclei (blue) of mesenchymal progenitor cells (MPCs) within the scar tissue; B, cotransplanted endothelial progenitor cells (EPCs; green) and MPCs (blue) in the border zone; C, evidence for endothelial differentiation of engrafted DAPI-positive EPCs (arrowheads) within vessels in the infarct; and D, evidence for cardiomyocyte differentiation of engrafted DAPI-positive MPCs (arrowheads) with coexpression of cardiac troponin T (green). Scale bar = 250 μm (A and B), 40 μm (C), and 30 μm (D). The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1249-1258DOI: (10.1016/j.jtcvs.2007.07.028) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 α-Smooth muscle actin (α-SMA) staining. A-D, Representative images of α-SMA staining in phosphate-buffered saline (PBS)–treated (A), mesenchymal progenitor cell (MPC)–treated (B), endothelial progenitor cell (EPC)–treated (C), and MPC/EPC-treated (D) hearts. Arrows indicate positive α-SMA staining in arterioles (note the many arterioles observed in EPC-treated hearts [C]), which was excluded from the calculation of myofibroblast density. E, The area of α-SMA staining (percentage of total area) representing myofibroblast density for the 4 treatment groups after transplantation. *P < .05 versus PBS; †P < .05 versus all other treatments. Scale bar = 150 μm. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1249-1258DOI: (10.1016/j.jtcvs.2007.07.028) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Connexin43 staining. A and B, Examples of connexin43 staining in border zone cardiomyocytes in phosphate-buffered saline (PBS)–treated (A) and endothelial progenitor cell (EPC)–treated (B) hearts. Scale bar = 50 μm. C, Intracellular connexin43 per myocyte in the infarct and peri-infarct areas for the 4 treatment groups. *P < .05 versus the PBS group. MPC, Mesenchymal progenitor cell. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1249-1258DOI: (10.1016/j.jtcvs.2007.07.028) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Vascular density. Representative α-smooth muscle actin–stained sections of infarct border zone territories showing the positively stained smooth muscle cells of arterioles in hearts that received phosphate-buffered saline (PBS; A), mesenchymal progenitor cell (MPC; B), endothelial progenitor cell (EPC; C), or MPC/EPC (D) treatment. Scale bar = 200 μm. E, The number of arterioles (per square millimeter) in the infarct and border zone for the 4 treatment groups. *P < .01 versus all other groups within territory (infarct or border zone); #P < .05 versus PBS-treated hearts. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1249-1258DOI: (10.1016/j.jtcvs.2007.07.028) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 Assessment of cardiac function. Left ventricular ejection fraction (LVEF; as a percentage; A); fractional shortening (FS; as a percentage; B), diastolic left ventricular internal dimension (LVID; in millimeters; C), and systolic LVID (in millimeters; D) at 0 and 28 days after treatment. *P < .05 versus all other treatments at day 28; †P < .05 versus phosphate-buffered saline (PBS) treatment at day 28; ‡P < .05 versus PBS and mesenchymal progenitor cell (MPC) treatment at day 28. EPC, Endothelial progenitor cell. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1249-1258DOI: (10.1016/j.jtcvs.2007.07.028) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions