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J Thorac Cardiovasc Surg 2009;138:646-653
© 2009 The American Association for Thoracic Surgery

Acquired Cardiovascular Disease

Cell therapy with autologous bone marrow mononuclear stem cells is associated with superior cardiac recovery compared with use of nonmodified mesenchymal stem cells in a canine model of chronic myocardial infarction

Myrielle Mathieu, DVMa,*, Jozef Bartunek, MD, PhDb,c, Bachar El Oumeiri, MDd, Karim Touihri, MDa, Ielham Hadad, MSa, Philippe Thoma, MDe, Thierry Metens, MS, PhDe, Agnes Mendes da Costa, DVMa, Maryam Mahmoudabady, MDa, Dominique Egrise, MS, PhDf, Didier Blocklet, MDf, Naïma Mazouz, MS, PhDg, Robert Naeije, MD, PhDa, Guy Heyndrickx, MD, PhDb,h, Kathleen McEntee, DVM, PhDa

a Department of Physiopathology, Faculty of Medicine, UBL, Brussels, Belgium
e Department of Radiology and Medical Imaging, Faculty of Medicine, UBL, Brussels, Belgium
f Department of Radio-Isotope Imaging, Faculty of Medicine, UBL, Brussels, Belgium
b Cardiovascular Center, OLV, Aalst, Belgium
c Faculty of Biomedical Engineering, TU Eindhoven, The Netherlands
d Cardio-Thoracic Surgery Department, Saint-Luc University Hospital, UCL, Brussels, Belgium
h Department of Physiology, Saint-Luc University Hospital, UCL, Brussels, Belgium
g Cardio3BioSciences, Braine L'Alleud, Belgium

Received for publication August 27, 2008; revisions received November 25, 2008; accepted for publication December 25, 2008.

* Address for reprints: Myrielle Mathieu, DVM, ULB–Erasme, 808 route de Lennik – CP604, 1070 Brussels, Belgium. (Email: myrielle.mathieu{at}ulb.ac.be).

Objective: Stem cell therapy can facilitate cardiac repair in infarcted myocardium, but the optimal cell type remains uncertain. We conducted a randomized, blind, and placebo-controlled comparison of autologous bone marrow mononuclear cell and mesenchymal stem cell therapy in a large-animal model of chronic myocardial infarction.

Methods: Eleven weeks after coronary ligation, 24 dogs received intramyocardial injections of mononuclear cells (227.106 ± 32.106 cells), mesenchymal stem cells (232.106 ± 40.106 cells), or placebo (n = 8 per group). Cardiac performance and remodeling were assessed up to 16 weeks' follow-up.

Results: At echocardiographic analysis, the wall motion score index showed a sustained improvement after mononuclear cell transfer (from 1.8 ± 0.1 to 1.5 ± 0.07) and a moderate late improvement after mesenchymal stem cell transfer (from 1.9 ± 0.08 to 1.7 ± 0.1). After mononuclear cell transfer, end-systolic elastance increased (from 2.23 ± 0.25 to 4.42 ± 0.55 mm Hg/mL), infarct size decreased (from 13% ± 0.67% to 10% ± 1.17%), N-terminal B-type natriuretic propeptide level decreased (from 608 ± 146 to 353 ± 118 pmol/L), and relative wall area and arterial density increased. Vascular endothelial growth factor receptor 2 expression was upregulated in the border zone. No change in cardiac contractility or histologic parameters was noted in the mesenchymal stem cell group.

Conclusion: In a canine model of chronic myocardial infarction, bone marrow mononuclear cell transfer is superior to mesenchymal stem cell transfer in improvement of cardiac contractility and regional systolic function and reduction in infarct size and plasma N-terminal B-type natriuretic propeptide level. Functional improvement is associated with a favorable angiogenic environment and neovascularization.

Abbreviations and Acronyms Ang = angiopoietin; BMNC = bone marrow mononuclear cell; Ct = cycle threshold; Ees = end-systolic elastance; LV = left ventricular; MI = myocardial infarction; MRI = magnetic resonance imaging; MSC = mesenchymal stem cell; RTQ-PCR = real-time quantification polymerase chain reaction; SDF-1 = stromal cell–derived factor 1; TEK = angiopoietin 1 and 2 receptor; VEGF = vascular endothelial growth factor; VEGFR = vascular endothelial growth factor receptor; WMS = wall motion score






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