Early improvement in cardiac tissue perfusion due to mesenchymal stem cells

Karl H. Schuleri, Luciano C. Amado, Andrew J. Boyle, Marco Centola, Anastasios P. Saliaris, Matthew R. Gutman, Konstantinos E. Hatzistergos, Behzad N. Oskouei, Jeffrey M. Zimmet, Randell G. Young, Alan W. Heldman, Albert C. Lardo, Joshua Hare

Research output: Contribution to journalArticle

123 Citations (Scopus)

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 languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number5
DOIs
StatePublished - May 1 2008

Fingerprint

Mesenchymal Stromal Cells
Left Ventricular Function
Perfusion
Swine
Myocardial Infarction
Placebos
Apoptosis
Injections
Magnetic Resonance Angiography
Reperfusion
Regeneration
Coronary Vessels
Magnetic Resonance Imaging
Therapeutics

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.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 294, No. 5, 01.05.2008.

Research output: Contribution to journalArticle

Schuleri, KH, Amado, LC, Boyle, AJ, Centola, M, Saliaris, AP, Gutman, MR, Hatzistergos, KE, Oskouei, BN, Zimmet, JM, Young, RG, Heldman, AW, Lardo, AC & Hare, J 2008, 'Early improvement in cardiac tissue perfusion due to mesenchymal stem cells', American Journal of Physiology - Heart and Circulatory Physiology, vol. 294, no. 5. https://doi.org/10.1152/ajpheart.00762.2007
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. / Early improvement in cardiac tissue perfusion due to mesenchymal stem cells. In: American Journal of Physiology - Heart and Circulatory Physiology. 2008 ; Vol. 294, No. 5.
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