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(Circulation. 2003;108:II-247.)
© 2003 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Transplantation of Autologous Fresh Bone Marrow Into Infarcted Myocardium: A Word of Caution

Alain Bel, MD; Emmanuel Messas, MD; Onnik Agbulut, PhD; Patrice Richard, MD; Jane- Lyse Samuel, PhD; Patrick Bruneval, MD; Albert A. Hagège, MD, PhD; Philippe Menasché, MD, PhD

From the Department of Cardiovascular Surgery, Hôpital Bichat (A.B.); the Department of Cardiology, Hôpital Européen Georges Pompidou & INSERM EMI-16 (E.M., A.A.H.); INSERM U-572, Hôpital Lariboisière (O.A., J.L.S.); the Laboratory of Hematopoietic Cell Biology & INSERM E00–03, Hôpital Saint-Louis (P.R.); the Department of Pathology & INSERM U-430, Hôpital Européen Georges Pompidou (P.B.); and the Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou (P.M.), Paris, France.

Correspondence to Philippe Menasché, MD, PhD, Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris. Phone: 33 1 56093622, Fax: 33 1 51092219, E-mail: philippe.menasche{at}hop.egp.ap-hop-paris.fr

Background— As the benefits of extemporaneous transplantation (Tx) of fresh (unfractionated) autologous bone marrow (BM) have been primarily studied in the setting of acute myocardial infarction, we assessed whether this approach could be effective for regenerating chronically infarcted myocardium.

Methods and Results— Myocardial infarction was created in 18 sheep by ligation of circumflex arterial branches. Three weeks later, BM was aspirated from the iliac crest, washed, labeled with the fluorescent dye Dil and reinjected (mean: 422x10⁶ cells in 3 mL) in 10 sites across the infarcted area through the reopened thoracotomy (n=9). Nine controls received culture medium. Left ventricular (LV) function was assessed before and 2 months after Tx by two-dimensional echocardiography whereas transmural velocity gradients were measured using M-mode tissue Doppler imaging at the center of the infarcted/grafted area. Formalin-fixed hearts were processed for the detection of grafted cells and angiogenesis. LV ejection fraction deteriorated similarly in the Tx and control groups (from 42±5% to 30±4% and from 40±4% to 31±1%, respectively; P=0.86). Likewise, BM Tx failed to prevent LV dilatation and impairment of the global wall motion score. The decrease in regional systolic velocity gradients (s^-1) featured a similar pattern (Tx group: from 0.77±0.11 to 0.31±0.07; control group: from 0.73±0.10 to 0.50±0.07; P=0.06). Histologically, there was neither BM tissue engraftment, except for a few scattered Dil-positive macrophages in the infarcted fibrotic areas nor transdifferentiation of BM cells into endothelial cells.

Conclusion— These data caution against the functional efficacy of extemporaneous Tx of fresh unfractionated BM into postinfarction scars.

Key Words: transplantation • stem cells • bone marrow • cell therapy • myocardial infarction