title: Cardiosphere-derived cells do not improve cardiac function in rats with cardiac failure.
abstract: Heart failure represents an important public health issue due to its high costs and growing incidence worldwide. Evidence showing the regenerative potential of postmitotic heart tissue has suggested the existence of endogenous cardiac stem cells in adult hearts. Cardiosphere-derived cells (CDC) constitute a candidate pool of such cardiac stem cells. Previous studies using acute myocardial infarction (MI) models in rodents demonstrated an improvement in cardiac function after cell therapy with CDC. We evaluated the therapeutic potential of CDC 60 days after MI in a rat model.
  
  
  
  CDC were obtained from human discarded myocardial tissue and rat hearts by enzymatic digestion with collagenase II. At 10-15 days after isolation, small, round, phase-bright cells (PBCs) appeared on top of the adherent fibroblast-like cells. The PBCs were collected and placed on a nonadherent plate for 2 days, where they formed cardiospheres which were then transferred to adherent plates, giving rise to CDC. These CDC were characterized by flow cytometry. Wistar rats were submitted to MI through permanent occlusion of the anterior descending coronary artery. After 60 days, they were immunosuppressed with cyclosporine A during 10 days. On the third day, infarcted animals were treated with 5 × 105human CDC (hCDC) or placebo through intramyocardial injection guided by echocardiogram. Another group of animals was treated with rat CDC (rCDC) without immunosuppression. hCDC and rCDC were stably transduced with a viral construct expressing luciferase under control of a constitutive promoter. CDC were then used in a bioluminescence assay. Functional parameters were evaluated by echocardiogram 90 and 120 days after MI and by Langendorff at 120 days.
  
  
  
  CDC had a predominantly mesenchymal phenotype. Cell tracking by bioluminescence demonstrated over 85% decrease in signal at 5-7 days after cell therapy. Cardiac function evaluation by echocardiography showed no differences in ejection fraction, end-diastolic volume, or end-systolic volume between groups receiving human cells, rat cells, or placebo. Hemodynamic analyses and infarct area quantification confirmed that there was no improvement in cardiac remodeling after cell therapy with CDC.
  
  
  
  Our study challenges the effectiveness of CDC in post-ischemic heart failure.
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.|National Institute of Cardiology, Rua das Laranjeiras, n°374-Laranjeiras, CEP:22240-006, Rio de Janeiro, RJ, Brazil.|National Center for Structural Biology and Bioimaging-CENABIO, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, buiding M, CEP:21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Taís Hanae
authors.initials: TH
authors.lastname: Kasai-Brunswick
authors.affiliation: National Institute of Cardiology, Rua das Laranjeiras, n°374-Laranjeiras, CEP:22240-006, Rio de Janeiro, RJ, Brazil.
authors.forename: Andréa Rodrigues da
authors.initials: AR
authors.lastname: Costa
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.|National Institute of Cardiology, Rua das Laranjeiras, n°374-Laranjeiras, CEP:22240-006, Rio de Janeiro, RJ, Brazil.
authors.forename: Raiana Andrade Quintanilha
authors.initials: RA
authors.lastname: Barbosa
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Farjun
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Fernanda Cristina Paccola
authors.initials: FC
authors.lastname: Mesquita
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Danúbia
authors.initials: D
authors.lastname: Silva Dos Santos
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.|National Center for Structural Biology and Bioimaging-CENABIO, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, buiding M, CEP:21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Isalira Peroba
authors.initials: IP
authors.lastname: Ramos
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Grazielle
authors.initials: G
authors.lastname: Suhett
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Guilherme Visconde
authors.initials: GV
authors.lastname: Brasil
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Sandro Torrentes da
authors.initials: ST
authors.lastname: Cunha
authors.affiliation: National Institute of Cardiology, Rua das Laranjeiras, n°374-Laranjeiras, CEP:22240-006, Rio de Janeiro, RJ, Brazil.
authors.forename: José Oscar R
authors.initials: JO
authors.lastname: Brito
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.|National Institute of Cardiology, Rua das Laranjeiras, n°374-Laranjeiras, CEP:22240-006, Rio de Janeiro, RJ, Brazil.
authors.forename: Juliana do Amaral
authors.initials: JD
authors.lastname: Passipieri
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil.|National Institute of Science and Technology for Regenerative Medicine, Av. Carlos Chagas Filho, n°373, CEP:21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Adriana Bastos
authors.initials: AB
authors.lastname: Carvalho
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, room G2-053, CEP:21941-902, Rio de Janeiro, RJ, Brazil. acarlos@biof.ufrj.br.|National Institute of Cardiology, Rua das Laranjeiras, n°374-Laranjeiras, CEP:22240-006, Rio de Janeiro, RJ, Brazil. acarlos@biof.ufrj.br.|National Center for Structural Biology and Bioimaging-CENABIO, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, n°373, buiding M, CEP:21941-902, Rio de Janeiro, RJ, Brazil. acarlos@biof.ufrj.br.|National Institute of Science and Technology for Regenerative Medicine, Av. Carlos Chagas Filho, n°373, CEP:21941-902, Rio de Janeiro, RJ, Brazil. acarlos@biof.ufrj.br.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Campos de Carvalho
mesh_terms: D000818:Animals; D054059:Coronary Occlusion / Q000000981:diagnostic imaging / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D016572:Cyclosporine / Q000008:administration & dosage; D004195:Disease Models, Animal; D004452:Echocardiography; D006334:Heart Function Tests; D006801:Humans; D016867:Immunocompromised Host; D015552:Injections, Intralesional; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D018874:Spheroids, Cellular / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D017211:Treatment Failure
chemical_list: D016572:Cyclosporine
keywords: Bioluminescence; Cardiosphere-derived cells; Cell therapy; Heart failure; Myocardial infarction; Stem cells