title: Can bone marrow-derived multipotent adult progenitor cells regenerate infarcted myocardium?
abstract: 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.
authors.affiliation: Inserm U633, Paris, France, Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie, Paris, France. onnik.agbulut@larib.inserm.fr
authors.forename: Onnik
authors.initials: O
authors.lastname: Agbulut
authors.forename: Manuel
authors.initials: M
authors.lastname: Mazo
authors.forename: Christophe
authors.initials: C
authors.lastname: Bressolle
authors.forename: María
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Kasra
authors.initials: K
authors.lastname: Azarnoush
authors.forename: Laurent
authors.initials: L
authors.lastname: Sabbah
authors.forename: Nicolas
authors.initials: N
authors.lastname: Niederlander
authors.forename: Gloria
authors.initials: G
authors.lastname: Abizanda
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Andreu
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelacho
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gavira
authors.forename: Maitane
authors.initials: M
authors.lastname: Perez-Ilzarbe
authors.forename: Séverine
authors.initials: S
authors.lastname: Peyrard
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Jane-Lyse
authors.initials: JL
authors.lastname: Samuel
authors.forename: Mario
authors.initials: M
authors.lastname: Soriano-Navarro
authors.forename: José M
authors.initials: JM
authors.lastname: García-Verdugo
authors.forename: Albert A
authors.initials: AA
authors.lastname: Hagège
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.forename: Philippe
authors.initials: P
authors.lastname: Menasché
mesh_terms: 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