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EXPRESS PUBLICATION

Comparison of human skeletal myoblasts and bone marrow-derived CD133⁺ progenitors for the repair of infarcted myocardium

Onnik Agbulut, PhD^*,*, Susanne Vandervelde^*, Nawwar Al Attar, MD^*, Jérôme Larghero, MD, Said Ghostine, MD, Bertrand Léobon, MD^||||, Estelle Robidel^*, Paolo Borsani, MD^*, Marc Le Lorc'h^¶¶, Alvine Bissery, PhD^||, Christine Chomienne, MD, PhD, Patrick Bruneval, MD, PhD^¶#, Jean-Pierre Marolleau, MD, Jean-Thomas Vilquin, PhD, Albert Hagège, MD, PhD, Jane-Lyse Samuel, PhD^* and Philippe Menasché, MD, PhD^**

^* Inserm U572, Hôpital Lariboisiére, Paris, France
Inserm U633, Hôpital Européen Georges Pompidou, Paris, France
Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France
^|| Clinical Investigation Center 9201, Hôpital Européen Georges Pompidou, Paris, France
^¶ Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France
^# Inserm U430, Hôpital Européen Georges Pompidou, Paris, France
^** Department of Cardiovascular Surgery, Hôpital Européen Georges PompidouParis, France
Inserm E0003, Paris, France
Laboratory of Cell Therapy, Hôpital Saint-LouisParis, France
Inserm U582, Paris, France
^|||| Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie; Paris, France
^¶¶ Department of Cytogenetics, Hôpital Necker, Paris, France

Manuscript received February 16, 2004; revised manuscript received March 26, 2004, accepted March 30, 2004.

^* Reprint requests and correspondence: Dr. Onnik Agbulut, Inserm U633, Laboratoire d'étude des greffes et prothèses car-diaques, 96, rue Didot, 75014, Paris, France.
onnik.agbulut{at}larib.inserm.fr

OBJECTIVES: The present study was designed as a face-to-face functional comparison of human skeletal myoblasts (SMs) and CD133⁺ bone marrow-derived hematopoietic progenitors in an animal model of semichronic myocardial infarction.

BACKGROUND: Compared with SMs, bone marrow-derived cells have the advantage of plasticity and might more effectively regenerate ischemic cardiac tissue. However, few data exist on the comparative efficacy of these two cell types in semichronic infarcts.

METHODS: A myocardial infarction was created by coronary ligation in 32 nude rats. Ten days later, rats received in-scar injections of human SMs, CD133⁺ progenitors, or culture medium. Left ventricular function was assessed before and one month after transplantation by echocardiography and pressure-volume loops. Immunofluorescence, polymerase chain reaction, and in situ hybridization were used to detect cells grafted in the hearts.

RESULTS: One month after transplantation, left ventricular ejection fraction decreased by 8 ± 4% in controls, whereas it increased by 7 ± 3% in CD133⁺-grafted hearts (p = 0.0015 vs. controls) and further by 15 ± 5% in SM-treated hearts (p = 0.008 vs. controls). Systolic indices yielded by pressure-volume loops paralleled these data. Engrafted myotubes were identified in all SM-treated hearts by immunofluorescence, whereas in CD133⁺-grafted hearts, few human cells were only detected by polymerase chain reaction.

CONCLUSIONS: In the setting of postinfarction scars, the transplantation of bone marrow-derived CD133⁺ progenitors improves cardiac function, but this benefit is not superior to that afforded by myogenic cells.

Abbreviations and Acronyms   FACS = fluorescence-activated cell sorting   HLA = human leukocyte antigen   LVEF = left ventricular ejection fraction   LV = left ventricular   mAb = monoclonal antibody   MyHC = myosin heavy chain   pAb = polyclonal antibody   PCR = polymerase chain reaction   SM = skeletal myoblast

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