Abstract
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.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 294 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2008 |
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Keywords
- Allogeneic
- Myocardial blood flow
- Myocardial infarction
- Neovascularization
- Perfusion magnetic resonance image
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
- Cardiology and Cardiovascular Medicine
Cite this
Early improvement in cardiac tissue perfusion due to mesenchymal stem cells. / Schuleri, Karl H.; Amado, Luciano C.; Boyle, Andrew J.; Centola, Marco; Saliaris, Anastasios P.; Gutman, Matthew R.; Hatzistergos, Konstantinos E.; Oskouei, Behzad N.; Zimmet, Jeffrey M.; Young, Randell G.; Heldman, Alan W.; Lardo, Albert C.; Hare, Joshua M.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 294, No. 5, 05.2008.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Early improvement in cardiac tissue perfusion due to mesenchymal stem cells
AU - Schuleri, Karl H.
AU - Amado, Luciano C.
AU - Boyle, Andrew J.
AU - Centola, Marco
AU - Saliaris, Anastasios P.
AU - Gutman, Matthew R.
AU - Hatzistergos, Konstantinos E.
AU - Oskouei, Behzad N.
AU - Zimmet, Jeffrey M.
AU - Young, Randell G.
AU - Heldman, Alan W.
AU - Lardo, Albert C.
AU - Hare, Joshua M.
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - Allogeneic
KW - Myocardial blood flow
KW - Myocardial infarction
KW - Neovascularization
KW - Perfusion magnetic resonance image
UR - http://www.scopus.com/inward/record.url?scp=44949240607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44949240607&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00762.2007
DO - 10.1152/ajpheart.00762.2007
M3 - Article
C2 - 18310523
AN - SCOPUS:44949240607
VL - 294
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 5
ER -