Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy

Karl H. Schuleri, Gary S. Feigenbaum, Marco Centola, Eric S. Weiss, Jeffrey M. Zimmet, Jennifer Turney, Joshua Kellner, Menekhem M. Zviman, Konstantinos E. Hatzistergos, Barbara Detrick, John V. Conte, Ian McNiece, Charles Jr Steenbergen, Albert C. Lardo, Joshua M. Hare

Research output: Contribution to journalArticle

Abstract

Aims The ability of mesenchymal stem cells (MSCs) to heal the chronically injured heart remains controversial. Here we tested the hypothesis that autologous MSCs can be safely injected into a chronic myocardial infarct scar, reduce its size, and improve ventricular function.Methods and resultsFemale adult Göttingen swine (n = 15) underwent left anterior descending coronary artery balloon occlusion to create reproducible ischaemia-reperfusion infarctions. Bone-marrow-derived MSCs were isolated and expanded from each animal. Twelve weeks post-myocardial infarction (MI), animals were randomized to receive surgical injection of either phosphate buffered saline (placebo, n = 6), 20 million (low dose, n = 3), or 200 million (high dose, n = 6) autologous MSCs in the infarct and border zone. Injections were administered to the beating heart via left anterior thoracotomy. Serial cardiac magnetic resonance imaging was performed to evaluate infarct size, myocardial blood flow (MBF), and left ventricular (LV) function. There was no difference in mortality, post-injection arrhythmias, cardiac enzyme release, or systemic inflammatory markers between groups. Whereas MI size remained constant in placebo and exhibited a trend towards reduction in low dose, high-dose MSC therapy reduced infarct size from 18.2 ± 0.9 to 14.4 ± 1.0 (P = 0.02) of LV mass. In addition, both low and high-dose treatments increased regional contractility and MBF in both infarct and border zones. Ectopic tissue formation was not observed with MSCs.ConclusionTogether these data demonstrate that autologous MSCs can be safely delivered in an adult heart failure model, producing substantial structural and functional reverse remodelling. These findings demonstrate the safety and efficacy of autologous MSC therapy and support clinical trials of MSC therapy in patients with chronic ischaemic cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)2722-2732
Number of pages11
JournalEuropean Heart Journal
Volume30
Issue number22
DOIs
StatePublished - Nov 2009

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Mesenchymal Stromal Cells
Cardiomyopathies
Cell- and Tissue-Based Therapy
Myocardial Infarction
Injections
Placebos
Balloon Occlusion
Choristoma
Ventricular Function
Thoracotomy
Left Ventricular Function
Infarction
Reperfusion
Cicatrix
Cardiac Arrhythmias
Coronary Vessels
Swine
Ischemia
Heart Failure
Bone Marrow

Keywords

  • Magnetic resonance imaging
  • Mesenchymal stem cells
  • Myocardial infarction
  • Remodelling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Schuleri, K. H., Feigenbaum, G. S., Centola, M., Weiss, E. S., Zimmet, J. M., Turney, J., ... Hare, J. M. (2009). Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. European Heart Journal, 30(22), 2722-2732. https://doi.org/10.1093/eurheartj/ehp265

Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. / Schuleri, Karl H.; Feigenbaum, Gary S.; Centola, Marco; Weiss, Eric S.; Zimmet, Jeffrey M.; Turney, Jennifer; Kellner, Joshua; Zviman, Menekhem M.; Hatzistergos, Konstantinos E.; Detrick, Barbara; Conte, John V.; McNiece, Ian; Steenbergen, Charles Jr; Lardo, Albert C.; Hare, Joshua M.

In: European Heart Journal, Vol. 30, No. 22, 11.2009, p. 2722-2732.

Research output: Contribution to journalArticle

Schuleri, KH, Feigenbaum, GS, Centola, M, Weiss, ES, Zimmet, JM, Turney, J, Kellner, J, Zviman, MM, Hatzistergos, KE, Detrick, B, Conte, JV, McNiece, I, Steenbergen, CJ, Lardo, AC & Hare, JM 2009, 'Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy', European Heart Journal, vol. 30, no. 22, pp. 2722-2732. https://doi.org/10.1093/eurheartj/ehp265
Schuleri KH, Feigenbaum GS, Centola M, Weiss ES, Zimmet JM, Turney J et al. Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. European Heart Journal. 2009 Nov;30(22):2722-2732. https://doi.org/10.1093/eurheartj/ehp265
Schuleri, Karl H. ; Feigenbaum, Gary S. ; Centola, Marco ; Weiss, Eric S. ; Zimmet, Jeffrey M. ; Turney, Jennifer ; Kellner, Joshua ; Zviman, Menekhem M. ; Hatzistergos, Konstantinos E. ; Detrick, Barbara ; Conte, John V. ; McNiece, Ian ; Steenbergen, Charles Jr ; Lardo, Albert C. ; Hare, Joshua M. / Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. In: European Heart Journal. 2009 ; Vol. 30, No. 22. pp. 2722-2732.
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