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J Thorac Cardiovasc Surg 2008;135:673-678
© 2008 The American Association for Thoracic Surgery
Cardiothoracic Transplantation |
a Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiovascular Surgery; University Paris-5, Faculty of Medicine, Paris, France
b Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Pathology; University Paris-5, Faculty of Medicine, INSERM U 872, Paris, France
c INSERM U 633, Laboratory of Biosurgical Research, Paris, France
d Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Epidemiology and Clinical Research Unit, INSERM CIE4, Paris, France
e Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Anesthesiology, Paris, France
f Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiovascular Surgery; University Paris-5, Faculty of Medicine, INSERM U 633, Paris, France
g Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiovascular Surgery; University Paris-5, Faculty of Medicine, Paris, France
Received for publication July 31, 2007; revisions received September 26, 2007; accepted for publication October 26, 2007. * Address for reprints: Philippe Menasché, MD, PhD, Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, 20, rue Leblanc, 75015 Paris, France. (Email: philippe.menasche{at}egp.aphp.fr).
Objective: Cardiac stem cell transplantation as a potential means of regenerating infarcted myocardium is currently receiving a great deal of interest. However, data on these endogenous cardiac precursors are primarily derived from animal studies, and their clinical relevance still remains elusive.
Methods: We prospectively screened 32 endomyocardial biopsies harvested from heart transplant recipients (off rejection episodes) and 18 right appendage biopsies collected during coronary artery bypass surgery, and processed the tissue specimens for the immunohistochemical detection of markers of stemness (c-kit, MDR-1, Isl-1), hematopoietic origin (CD45), mast cells (tryptase), endothelial cells (CD105), and cardiac lineage (Nkx2.5). Confocal microscopy was used for colocalization experiments. Three right appendage biopsies were also cultured for 2 to 3 weeks, at the completion of which c-kit–positive cells were sorted by flow cytometry.
Results: In endomyocardial biopsies, a median number of 2.7 (1.8–4) c-kit–positive cells/mm2 were found, and this number was even significantly smaller in right appendage biopsies (1 [0.5–1.8] c-kit–positive cell/mm2, P = .01). All of these c-kit–positive cells co-stained for CD45 and were more specifically identified as mast cells by their positive staining for the specific tryptase marker. However, none of the c-kit–positive cells expressed the markers of stemness MDR-1 and Isl-1 or colocalized with CD105. Flow cytometry confirmed the small number of c-kit–positive cells in cultured right atrial appendages.
Conclusion: These data raise a cautionary note on the therapeutic exploitation of cardiac stem cells in patients with ischemic cardiomyopathy, who may be the elective candidates for regenerative therapy.
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