Can bone marrow-derived multipotent adult progenitor cells regenerate infarcted myocardium?
OBJECTIVE
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 (5 x 10(6) cells/150 microL) 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 Resovist 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.
Agbulut
Onnik
O
Inserm U633, Paris, France, Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie, Paris, France. onnik.agbulut@larib.inserm.fr
Mazo
Manuel
M
Bressolle
Christophe
C
Gutierrez
María
M
Azarnoush
Kasra
K
Sabbah
Laurent
L
Niederlander
Nicolas
N
Abizanda
Gloria
G
Andreu
Enrique J
EJ
Pelacho
Beatriz
B
Gavira
Juan J
JJ
Perez-Ilzarbe
Maitane
M
Peyrard
Séverine
S
Bruneval
Patrick
P
Samuel
Jane-Lyse
JL
Soriano-Navarro
Mario
M
García-Verdugo
José M
JM
Hagège
Albert A
AA
Prósper
Felipe
F
Menasché
Philippe
P
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D005260:Female; D006084:Graft Rejection; D023421:Models, Animal; D039902:Multipotent Stem Cells / Q000637:transplantation* / Q000648:ultrastructure; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017211:Treatment Failure