title: Delayed administration of allogeneic cardiac stem cell therapy for acute myocardial infarction could ameliorate adverse remodeling: experimental study in swine.
abstract: BACKGROUND
  The optimal timing of cardiac stem cells administration is still unclear. We assessed the safety of same-day and delayed (one week) delivery and the possible influence of the timing on the therapeutic outcomes of allogeneic porcine cardiac stem cells administration after acute myocardial infarction in a closed-chest ischemia-reperfusion model.
  
  
  METHODS
  Female swine surviving 90 min occlusion of the mid left anterior descending coronary artery received an intracoronary injection of 25x10(6) porcine cardiac stem cells either two hours (n = 5, D0) or 7 days (n = 6, D7) after reperfusion. Controls received intracoronary injection of vehicle on day 7 (n = 6, CON). Safety was defined in terms of absence of major cardiac events, changes to the ECG during injection, post-administration coronary flow assessed using the TIMI scale and cardiac troponin I determination after the intervention. Cardiac Magnetic Resonance was performed for morphological and functional assessment prior to infarction, before injection (D7 and CON groups only), at one and 10 weeks. Samples were taken from the infarct and transition areas for pathological examination.
  
  
  RESULTS
  No major adverse cardiac events were seen during injection in any group. Animals receiving the therapy on the same day of infarction (D0 group) showed mild transient ST changes during injection (n = 4) and, in one case, slightly compromised coronary flow (TIMI 2). Cardiac function parameters and infarct sizes were not significantly different between groups, with a trend towards higher ejection fraction in the treated groups. Ventricular volumes indexed to body surface area increased over time in control animals, and decreased by the end of the study in animals receiving the therapy, significantly so when comparing End Diastolic Volume between CON and D7 groups (CON: 121.70 ml/m(2) ± 26.09 ml/m(2), D7: 98.71 ml/m(2) ± 8.30 ml/m(2), p = 0.037). The treated groups showed less organization of the collagenous scar, and a significantly (p = 0.019) higher amount of larger, more mature vessels at the infarct border.
  
  
  CONCLUSIONS
  The intracoronary injection of 25x10(6) allogeneic cardiac stem cells is generally safe, both early and 7 days after experimental infarction, and alleviates myocardial dysfunction, with a greater limitation of left ventricular remodeling when performed at one week.
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Carretera N-521, km 41.8, 10071, Cáceres, Spain. crisosto@ccmijesususon.com.
authors.forename: Veronica
authors.initials: V
authors.lastname: Crisostomo
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Carretera N-521, km 41.8, 10071, Cáceres, Spain. cbaez@ccmijesususon.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Baez-Diaz
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Carretera N-521, km 41.8, 10071, Cáceres, Spain. jmaestre@ccmijesususon.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Maestre
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Carretera N-521, km 41.8, 10071, Cáceres, Spain. mgarcia@ccmijesususon.com.
authors.forename: Monica
authors.initials: M
authors.lastname: Garcia-Lindo
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Carretera N-521, km 41.8, 10071, Cáceres, Spain. feisun@ccmijesususon.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Carretera N-521, km 41.8, 10071, Cáceres, Spain. jgarcia@ccmijesususon.com.
authors.forename: Javier G
authors.initials: JG
authors.lastname: Casado
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Carretera N-521, km 41.8, 10071, Cáceres, Spain. rblazquez@ccmijesususon.com.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Blazquez
authors.affiliation: Coretherapix, Santiago Grisolía, n° 2 Parque Científico de Madrid, 28760, Tres Cantos, Madrid, Spain. jlabad@coretherapix.com.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Abad
authors.affiliation: Coretherapix, Santiago Grisolía, n° 2 Parque Científico de Madrid, 28760, Tres Cantos, Madrid, Spain. ipalacios@coretherapix.com.
authors.forename: Itziar
authors.initials: I
authors.lastname: Palacios
authors.affiliation: Coretherapix, Santiago Grisolía, n° 2 Parque Científico de Madrid, 28760, Tres Cantos, Madrid, Spain. lrodriguez@coretherapix.com.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodriguez-Borlado
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Carretera N-521, km 41.8, 10071, Cáceres, Spain. msanchez@ccmijesususon.com.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Sanchez-Margallo
mesh_terms: D000818:Animals; D005260:Female; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D000069236:Pericardial Fluid; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D034421:Sus scrofa; D013997:Time Factors; D014184:Transplantation, Homologous; D014336:Troponin / Q000378:metabolism; D020257:Ventricular Remodeling; D014998:Y Chromosome / Q000378:metabolism
chemical_list: D014336:Troponin