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J Thorac Cardiovasc Surg 2007;134:565-573
© 2007 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Bone marrow–derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site

^a Department of Surgery, Clinical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
^b Department of Cardiology, Clinical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
^c Department of Pathology, Clinical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
^d Department of Anaesthesiology, Clinical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland.

Received for publication February 25, 2007; revisions received April 18, 2007; accepted for publication May 2, 2007.

^_* Address for reprints: Professor Tatu Juvonen, Department of Surgery, Oulu University Hospital, PO Box 21, 90029 Oulu, Finland. (Email: Tatu.juvonen{at}oulu.fi).

Objective: Stem cell therapy in myocardial infarction is under intensive investigation; however, the mechanisms of recovery and the optimal transplantation technique remain controversial. The goal of this controlled and randomized study was to test the hypothesis that locally injected bone marrow–derived mononuclear cells can focus in on the damaged myocardium and improve cardiac function by means of active participation in remodeling.

Methods: Myocardial infarction was introduced through occlusion of the circumflex coronary artery for 90 minutes in 14 piglets (24.0 ± 4.9 kg) that were randomized to a cell-therapy group (n = 7) and a control group (n = 7). At reperfusion, autologous purified prelabeled or unlabeled cells (10⁸ cells/2 mL) or saline were injected into the myocardium. Cardiac function was measured by using echocardiography preoperatively and postoperatively and at 3 weeks, when hearts were collected for histopathologic examination.

Results: The ejection fraction recovered in the cell-therapy group (P = .02) but failed to recover in the control group, and at 3 weeks, it remained at the lower level compared with that in the cell-therapy group (P = .067). The number of living cells in the necrotic area was significantly greater in the cell-therapy group (P < .001). Labeled cells were detected in the infarcted area, and they showed signs of myocyte differentiation. Furthermore, the proportional area of muscle actin-positive cells at the granulation area was higher in the cell-therapy group (P = .035).

Conclusions: Autologous bone marrow–derived mononuclear cells at the infarcted area localize in the myocardium. The exact mechanism of recovery remains to be determined, but our findings may give new information concerning the cellular events that occur during cell therapy–enhanced recovery.