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J Thorac Cardiovasc Surg 2005;130:1310
© 2005 The American Association for Thoracic Surgery
Cardiopulmonary Support and Physiology |
Division of Cardiac Surgery, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
Read at the C. Walton Lillehei Resident Competition at the Eighty-fifth Annual Meeting of The American Association for Thoracic Surgery, San Francisco, Calif, April 10-13, 2005.
Received for publication April 7, 2005; revisions received June 30, 2005; accepted for publication July 19, 2005. * Address for reprints: Ren-Ke Li, MD, PhD, NU 1-115, 200 Elizabeth Street, Toronto General Hospital, Toronto, Ontario, Canada M5G-2C4 (Email: renkeli{at}uhnres.utoronto.ca).
OBJECTIVE: We hypothesized that implantation of adult mesenchymal stem cells after acute myocardial infarction mobilizes bone marrow precursor cells by activating the stem cell factor pathway, and that overdriving this pathway would enhance the beneficial effects of cell transplantation.
METHODS: After coronary ligation, medium, mesenchymal stem cells, or stem cell factor–overproducing mesenchymal stem cells were injected into the anterior left ventricle. Cells from ß-galactosidase transgenic mice enabled tracking of injected cells. The global and local impact of the cells was evaluated by measuring cytokine levels, endothelial progenitor cells, and myocardial angiogenesis, and by addressing cardiomyogenesis with confocal microscopy. The impact on cardiac function was evaluated by pressure-volume loops. Ventricular morphometrics were measured after in situ perfusion-fixation of the hearts at physiologic pressures.
RESULTS: Implantation of mesenchymal stem cells increased myocardial stem cell factor levels 2.0-fold, endothelial progenitor cell mobilization 2.7-fold, and myocardial angiogenesis 2.3-fold (P < .05), but did not induce mitogenesis in host cardiomyocytes or give rise to ß-galactosidase–expressing cardiomyocytes. Cell-transplanted groups had improved indices of cardiac function, including preload recruitable stroke work and end-systolic elastance (P < .001). Cell transplantation resulted in 2.0-fold smaller ventricular volumes (P = .001) and 2.0-fold reduced infarct scar area (P = .056), but had no effect on the volume of spared myocardium. Stem cell factor overproduction imparted greater functional benefit without inducing detectable histologic cardiomyocyte regeneration.
CONCLUSION: Mesenchymal stem cell implantation after myocardial infarction facilitates functional cardiac regeneration without myocyte regeneration through augmentation of endogenous infarct repair, which is enhanced by stem cell factor.
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