title: Right ventricular failure secondary to chronic overload in congenital heart diseases: benefits of cell therapy using human embryonic stem cell-derived cardiac progenitors.
abstract: OBJECTIVE
  Despite the increasing incidence of right ventricular (RV) failure in adult patients with congenital heart disease, current therapeutic options are still limited. By contrast to left-heart diseases, cell-based myocardial regeneration applied to the right ventricle is poorly studied, even though it may be a therapeutic solution. As human embryonic stem cell-derived cardiac progenitors seem to be good candidates owing to their proliferation capacity, our aim was to assess, in a large animal model of overloaded RV dysfunction, the feasibility and effects of such a cell therapy.
  
  
  METHODS
  Human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells were administered using multiple intramyocardial injections 4 months after a surgical procedure mimicking the repaired tetralogy of Fallot, and their effects were observed 3 months later on hemodynamic, rhythmic, and histologic parameters.
  
  
  RESULTS
  All pigs (sham n = 6, treated n = 6) survived without complication, and cell therapy was clinically well tolerated. Although functional, contractility, and energetics parameters evolved similarly in both groups, benefits regarding arrhythmic susceptibility were observed in the treated group, associated with a significant decrease of peri-myocyte fibrosis (5.71% ± 2.49% vs 12.12% ± 1.85%; P < .01) without interstitial fibrosis change (5.18% ± 0.81% vs 5.49% ± 1.01%). Such a decrease could be related to paracrine effects, as no human cells could be detected within the myocardium.
  
  
  CONCLUSIONS
  Cell therapy using intramyocardial injections of human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells seems to have benefits regarding overloaded RV tissue remodeling and arrhythmic susceptibility, but this mode of administration is not sufficient to obtain a significant improvement in RV function.
authors.affiliation: Medical Research Department, Centre Chirurgical Marie Lannelongue, Inserm UMR_S999, LabEx LERMIT, Le Plessis-Robinson, France; Université Paris Sud, DHU Thorax Innovation, Le Kremlin-Bicêtre, France; Department of Pediatric and Congenital Heart Diseases, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France. Electronic address: v.lambert@ccml.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lambert
authors.affiliation: Medical Research Department, Centre Chirurgical Marie Lannelongue, Inserm UMR_S999, LabEx LERMIT, Le Plessis-Robinson, France; Université Paris Sud, DHU Thorax Innovation, Le Kremlin-Bicêtre, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Gouadon
authors.affiliation: Medical Research Department, Centre Chirurgical Marie Lannelongue, Inserm UMR_S999, LabEx LERMIT, Le Plessis-Robinson, France; Université Paris Sud, DHU Thorax Innovation, Le Kremlin-Bicêtre, France.
authors.forename: André
authors.initials: A
authors.lastname: Capderou
authors.affiliation: Department of Pediatric and Congenital Heart Diseases, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Le Bret
authors.affiliation: Department of Pediatric and Congenital Heart Diseases, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ly
authors.affiliation: Département de Cardiologie, Centre Hospitalier Antoine Béclère, Clamart, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dinanian
authors.affiliation: Medical Research Department, Centre Chirurgical Marie Lannelongue, Inserm UMR_S999, LabEx LERMIT, Le Plessis-Robinson, France; Université Paris Sud, DHU Thorax Innovation, Le Kremlin-Bicêtre, France.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Renaud
authors.affiliation: Inserm UMR_S910, Faculté de Médecine de la Timone, Marseille, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Pucéat
authors.affiliation: Medical Research Department, Centre Chirurgical Marie Lannelongue, Inserm UMR_S999, LabEx LERMIT, Le Plessis-Robinson, France; Université Paris Sud, DHU Thorax Innovation, Le Kremlin-Bicêtre, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rücker-Martin
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D015415:Biomarkers / Q000378:metabolism; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002460:Cell Line; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000637:transplantation*; D005240:Feasibility Studies; D005355:Fibrosis; D006439:Hemodynamics; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000637:transplantation*; D020127:Recovery of Function; D012038:Regeneration; D013552:Swine; D013771:Tetralogy of Fallot / Q000150:complications / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D016278:Ventricular Function, Right; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers