Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties

Matthew J. Price, Chung Chuan Chou, Malka Frantzen, Takashi Miyamoto, Saibal Kar, Steve Lee, Prediman K. Shah, Bradley J. Martin, Michael Lill, James S. Forrester, Peng-Sheng Chen, Raj R. Makkar

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [n = 7] had significantly higher LVEF than controls [n = 8] (49 ± 2% vs. 44 ± 3%, P = 0.015)and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths (P ≤ 0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium. Conclusion: IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalInternational Journal of Cardiology
Volume111
Issue number2
DOIs
StatePublished - Aug 10 2006
Externally publishedYes

Fingerprint

Cell- and Tissue-Based Therapy
Mesenchymal Stromal Cells
Left Ventricular Function
Stroke Volume
Myocardial Infarction
Myocardium
Swine
Reperfusion
Atrial Remodeling
Balloon Occlusion
Ventricular Remodeling
Infarction
Cardiac Arrhythmias
Stem Cells
Bone Marrow
Lung
Injections

Keywords

  • Apical infarction
  • Occlusion
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. / Price, Matthew J.; Chou, Chung Chuan; Frantzen, Malka; Miyamoto, Takashi; Kar, Saibal; Lee, Steve; Shah, Prediman K.; Martin, Bradley J.; Lill, Michael; Forrester, James S.; Chen, Peng-Sheng; Makkar, Raj R.

In: International Journal of Cardiology, Vol. 111, No. 2, 10.08.2006, p. 231-239.

Research output: Contribution to journalArticle

Price, Matthew J. ; Chou, Chung Chuan ; Frantzen, Malka ; Miyamoto, Takashi ; Kar, Saibal ; Lee, Steve ; Shah, Prediman K. ; Martin, Bradley J. ; Lill, Michael ; Forrester, James S. ; Chen, Peng-Sheng ; Makkar, Raj R. / Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. In: International Journal of Cardiology. 2006 ; Vol. 111, No. 2. pp. 231-239.
@article{5dbad2dffd5f44e1a53b059fd8b90aae,
title = "Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties",
abstract = "Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [n = 7] had significantly higher LVEF than controls [n = 8] (49 ± 2{\%} vs. 44 ± 3{\%}, P = 0.015)and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths (P ≤ 0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium. Conclusion: IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.",
keywords = "Apical infarction, Occlusion, Reperfusion",
author = "Price, {Matthew J.} and Chou, {Chung Chuan} and Malka Frantzen and Takashi Miyamoto and Saibal Kar and Steve Lee and Shah, {Prediman K.} and Martin, {Bradley J.} and Michael Lill and Forrester, {James S.} and Peng-Sheng Chen and Makkar, {Raj R.}",
year = "2006",
month = "8",
day = "10",
doi = "10.1016/j.ijcard.2005.07.036",
language = "English (US)",
volume = "111",
pages = "231--239",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties

AU - Price, Matthew J.

AU - Chou, Chung Chuan

AU - Frantzen, Malka

AU - Miyamoto, Takashi

AU - Kar, Saibal

AU - Lee, Steve

AU - Shah, Prediman K.

AU - Martin, Bradley J.

AU - Lill, Michael

AU - Forrester, James S.

AU - Chen, Peng-Sheng

AU - Makkar, Raj R.

PY - 2006/8/10

Y1 - 2006/8/10

N2 - Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [n = 7] had significantly higher LVEF than controls [n = 8] (49 ± 2% vs. 44 ± 3%, P = 0.015)and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths (P ≤ 0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium. Conclusion: IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.

AB - Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [n = 7] had significantly higher LVEF than controls [n = 8] (49 ± 2% vs. 44 ± 3%, P = 0.015)and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths (P ≤ 0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium. Conclusion: IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.

KW - Apical infarction

KW - Occlusion

KW - Reperfusion

UR - http://www.scopus.com/inward/record.url?scp=33746302842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746302842&partnerID=8YFLogxK

U2 - 10.1016/j.ijcard.2005.07.036

DO - 10.1016/j.ijcard.2005.07.036

M3 - Article

VL - 111

SP - 231

EP - 239

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

IS - 2

ER -