TY - JOUR
T1 - Comparative effects of mesenchymal progenitor cells, endothelial progenitor cells, or their combination on myocardial infarct regeneration and cardiac function
AU - Suuronen, Erik J.
AU - Price, Joel
AU - Veinot, John P.
AU - Ascah, Kathryn
AU - Kapila, Varun
AU - Guo, Xue Wei
AU - Wong, Serena
AU - Mesana, Thierry G.
AU - Ruel, Marc
N1 - Funding Information:
Supported by award 7346 from the Canadian Foundation for Innovation (to Dr Ruel), by grant MOP-77536 from the Canadian Institutes of Health Research (to Drs Ruel and Suuronen), and by a Heart and Stroke Foundation of Canada/AstraZeneca Canada, Inc, Fellowship (to Dr Suuronen).
PY - 2007/11
Y1 - 2007/11
N2 - Objective: Recent evidence suggests that the effects of mesenchymal progenitor cell transplantation into the infarcted myocardium might be mediated by local paracrine angiogenesis. We compared the effects of mesenchymal progenitor cell transplantation versus those of a primarily angiogenic cell, the endothelial progenitor cell, in a rat model of myocardial infarction. Methods: Twenty-one days after left anterior descending artery ligation, rats were injected in their infarcted anterior myocardium with 1 × 106 mesenchymal progenitor cells, 1 × 106 endothelial progenitor cells, 5 × 105 mesenchymal progenitor cells plus 5 × 105 endothelial progenitor cells, or phosphate-buffered saline (n = 6-8 per group). Echocardiography was performed before injection and 4 weeks later, after which rats were killed and immunohistochemical analyses performed. Results: Connexin43 density was greater in cell-treated groups compared with that seen in the phosphate-buffered saline group (by 91.6% ± 15.2%, P < .001), with no observed difference between cell-treated groups (P ≥ .3). Endothelial progenitor cell treatment increased arteriolar density within the infarct border zone (by 297%, 205%, and 101% vs phosphate-buffered saline, mesenchymal progenitor cell, and mesenchymal progenitor cell/endothelial progenitor cell treatment, respectively; P < .01). Postoperative left ventricular ejection fraction (endothelial progenitor cell: 68.3% ± 9.8% vs mesenchymal progenitor cell/endothelial progenitor cell: 55.0% ± 11.1%, mesenchymal progenitor cell: 53.0% ± 6.0%, and phosphate-buffered saline: 49.6% ± 9.5%) and fractional shortening (endothelial progenitor cell: 32.4% ± 5.1% vs mesenchymal progenitor cell: 22.5% ± 5.4% and phosphate-buffered saline: 21.3% ± 5.3%) were greater in endothelial progenitor cell-treated rats versus those receiving other treatments (all P < .05). Only endothelial progenitor cells prevented further contractile deterioration compared with baseline values (P = .8), whereas other groups had continued loss of function after treatment. Conclusion: Compared with the use of mesenchymal progenitor cells, cell transplantation with endothelial progenitor cells after myocardial infarction resulted in better neovascularization and contractility. This suggests that angiogenesis is an important mechanism in attenuating the progression of left ventricular dysfunction after myocardial infarction.
AB - Objective: Recent evidence suggests that the effects of mesenchymal progenitor cell transplantation into the infarcted myocardium might be mediated by local paracrine angiogenesis. We compared the effects of mesenchymal progenitor cell transplantation versus those of a primarily angiogenic cell, the endothelial progenitor cell, in a rat model of myocardial infarction. Methods: Twenty-one days after left anterior descending artery ligation, rats were injected in their infarcted anterior myocardium with 1 × 106 mesenchymal progenitor cells, 1 × 106 endothelial progenitor cells, 5 × 105 mesenchymal progenitor cells plus 5 × 105 endothelial progenitor cells, or phosphate-buffered saline (n = 6-8 per group). Echocardiography was performed before injection and 4 weeks later, after which rats were killed and immunohistochemical analyses performed. Results: Connexin43 density was greater in cell-treated groups compared with that seen in the phosphate-buffered saline group (by 91.6% ± 15.2%, P < .001), with no observed difference between cell-treated groups (P ≥ .3). Endothelial progenitor cell treatment increased arteriolar density within the infarct border zone (by 297%, 205%, and 101% vs phosphate-buffered saline, mesenchymal progenitor cell, and mesenchymal progenitor cell/endothelial progenitor cell treatment, respectively; P < .01). Postoperative left ventricular ejection fraction (endothelial progenitor cell: 68.3% ± 9.8% vs mesenchymal progenitor cell/endothelial progenitor cell: 55.0% ± 11.1%, mesenchymal progenitor cell: 53.0% ± 6.0%, and phosphate-buffered saline: 49.6% ± 9.5%) and fractional shortening (endothelial progenitor cell: 32.4% ± 5.1% vs mesenchymal progenitor cell: 22.5% ± 5.4% and phosphate-buffered saline: 21.3% ± 5.3%) were greater in endothelial progenitor cell-treated rats versus those receiving other treatments (all P < .05). Only endothelial progenitor cells prevented further contractile deterioration compared with baseline values (P = .8), whereas other groups had continued loss of function after treatment. Conclusion: Compared with the use of mesenchymal progenitor cells, cell transplantation with endothelial progenitor cells after myocardial infarction resulted in better neovascularization and contractility. This suggests that angiogenesis is an important mechanism in attenuating the progression of left ventricular dysfunction after myocardial infarction.
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U2 - 10.1016/j.jtcvs.2007.07.028
DO - 10.1016/j.jtcvs.2007.07.028
M3 - Article
C2 - 17976457
AN - SCOPUS:35448930673
SN - 0022-5223
VL - 134
SP - 1249
EP - 1258
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 5
ER -