Copyright © 2006, European Society of Cardiology
Can bone marrow-derived multipotent adult progenitor cells regenerate infarcted myocardium?
aInserm U633, Paris, France, Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie, Paris, France
bHematology, Cardiology and Cell Therapy, Clínica Universitaria and Division of Cancer, Foundation for Applied Medical Research, Division of Cancer, University of Navarra, Pamplona, Spain
cUniversity Paris 7, Department of Biochemistry, Paris, France
dAssistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiology, University Paris-5, Faculty of Medicine, Paris, France, INSERUM U 633, France
eCRBM, CNRS FRE2593, Montpellier, France
fInserm and Clinical Investigation Center, Hôpital Européen Georges Pompidou, Paris, France
gAssistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Pathology, University of Paris 5, Faculty of Medicine, Paris, France, INSERUM U 430, France
hInserm U689, Paris, France
iInstituto Cavanilles, University of Valencia, Valencia, Spain
jAssistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiovascular Surgery, University of Paris-5, Faculty of Medicine, INSERUM U633, Paris, France
* Correspondings author. Prósper is to be contacted at Hematology and Cell Therapy, Clinica Universitaria, Av Pio XII 36, Pamplona 31008, Spain. Tel.: +34 948 255 400. Agbulut, Inserm U633, Laboratoire d'étude des greffes et prothèses cardiaques, 96, rue Didot, 75014, Paris, France. Tel.: +33 1 4395 9360; fax: +33 1 4540 5049. Email address: onnik.agbulut{at}larib.inserm.fr fprosper{at}unav.es
Objectives: To assess the functional effects of multipotent adult progenitor cells (MAPCs) transplanted in a rat model of chronic myocardial infarction.
Methods: Forty-four rats underwent coronary ligation and, 14 days later, were randomly allocated to receive in-scar injections (5x106 cells/150 µL) of green fluorescent protein (eGFP)-transduced allogeneic MAPCs (n=25) or culture medium (controls, n=19). Nine of the MAPC-treated hearts were employed for functional studies while the remaining 16 received cells co-labeled with ResovistTM and were only used for serial histological assessments. Left ventricular (LV) function was assessed echocardiographically before transplantation and 1 month thereafter in a blinded manner. Immunohistochemistry, electron microscopy and PCR were used to detect grafted cells. All data were compared by nonparametric tests.
Results: Baseline ejection fractions (EF, median;[interquartile range]) did not differ significantly among the groups: 30% [0.23;0.37] and 37% [0.32;0.38] in control and rMAPC-transplanted hearts, respectively. One month later, LV function of control hearts was found to have deteriorated, as reflected by a decline in EF to 24% [0.21;0.30], and although EF tended to remain more stable after cell transplantation (37% [0.27;0.41]), the difference between the two groups failed to achieve statistical significance (p=0.06). While MAPCs could be identified early post-transplant, no evidence of engraftment was further observed at 1 month by immunohistochemistry, electron microscopy or PCR.
Conclusions: In this model, MAPCs did not improve global pump function, and although some of these cells expressed endothelial markers during the early post-transplant period, we could not detect any evidence for differentiation into cardiomyocytes and no engraftment was further identified beyond 2 weeks after cell injections.
KEYWORDS Progenitor cells; Bone marrow; Transplantation; Myocardial infarction; MAPCs
1 OA and MM contribute equally to this manuscript.