Early improvement in cardiac tissue perfusion due to mesenchymal stem cells
| Autor: | Alan W. Heldman, Karl H. Schuleri, Matthew R Gutman, Anastasios Saliaris, Andrew J. Boyle, Randell G. Young, Marco Centola, Luciano C. Amado, Albert C. Lardo, Joshua M. Hare, Behzad N. Oskouei, Jeffrey M. Zimmet, Konstantinos E. Hatzistergos |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Swine Physiology Myocardial Infarction Hemodynamics Apoptosis Mesenchymal Stem Cell Transplantation Ventricular Function Left Neovascularization Coronary Circulation Physiology (medical) Internal medicine Animals Regeneration Transplantation Homologous Medicine Myocardial infarction business.industry Myocardium Mesenchymal stem cell Recovery of Function Blood flow medicine.disease Coronary Vessels Magnetic Resonance Imaging Surgery Disease Models Animal Regional Blood Flow Circulatory system Cardiology Female Stem cell medicine.symptom Cardiology and Cardiovascular Medicine business Perfusion |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 294:H2002-H2011 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00762.2007 |
| Popis: | The underlying mechanism(s) of improved left ventricular function (LV) due to mesenchymal stem cell (MSC) administration after myocardial infarction (MI) remains highly controversial. Myocardial regeneration and neovascularization, which leads to increased tissue perfusion, are proposed mechanisms. Here we demonstrate that delivery of MSCs 3 days after MI increased tissue perfusion in a manner that preceded improved LV function in a porcine model. MI was induced in pigs by 60-min occlusion of the left anterior descending coronary artery, followed by reperfusion. Pigs were assigned to receive intramyocardial injection of allogeneic MSCs (200 million, ∼15 injections) ( n = 10), placebo ( n = 6), or no intervention ( n = 8). Resting myocardial blood flow (MBF) was serially assessed by first-pass perfusion magnetic resonance imaging (MRI) over an 8-wk period. Over the first week, resting MBF in the infarct area of MSC-treated pigs increased compared with placebo-injected and untreated animals [0.17 ± 0.03, 0.09 ± 0.01, and 0.08 ± 0.01, respectively, signal intensity ratio of MI to left ventricular blood pool (LVBP); P < 0.01 vs. placebo, P < 0.01 vs. nontreated]. In contrast, the signal intensity ratios of the three groups were indistinguishable at weeks 4 and 8. However, MSC-treated animals showed larger, more mature vessels and less apoptosis in the infarct zones and improved regional and global LV function at week 8. Together these findings suggest that an early increase in tissue perfusion precedes improvements in LV function and a reduction in apoptosis in MSC-treated hearts. Cardiac MRI-based measures of blood flow may be a useful tool to predict a successful myocardial regenerative process after MSC treatment. |
| Databáze: | OpenAIRE |
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