title: Improvement of cardiac function by placenta-derived mesenchymal stem cells does not require permanent engraftment and is independent of the insulin signaling pathway.
abstract: BACKGROUND
  The objective of this work was to evaluate the efficacy of placenta-derived mesenchymal stem cell (MSC) therapy in a mouse model of myocardial infarction (MI). Since MSCs can be obtained from two different regions of the human term placenta (chorionic plate or villi), cells obtained from both these regions were compared so that the best candidate for cell therapy could be selected.
  
  
  METHODS
  For the in vitro studies, chorionic plate MSCs (cp-MSCs) and chorionic villi MSCs (cv-MSCs) were extensively characterized for their genetic stability, clonogenic and differentiation potential, gene expression, and immunophenotype. For the in vivo studies, C57Bl/6 mice were submitted to MI and, after 21 days, received weekly intramyocardial injections of cp-MSCs for 3 weeks. Cells were also stably transduced with a viral construct expressing luciferase, under the control of the murine stem cell virus (MSCV) promoter, and were used in a bioluminescence assay. The expression of genes associated with the insulin signaling pathway was analyzed in the cardiac tissue from cp-MSCs and placebo groups.
  
  
  RESULTS
  Morphology, differentiation, immunophenotype, and proliferation were quite similar between these cells. However, cp-MSCs had a greater clonogenic potential and higher expression of genes related to cell cycle progression and genome stability. Therefore, we considered that the chorionic plate was preferable to the chorionic villi for the isolation of MSCs. Sixty days after MI, cell-treated mice had a significant increase in ejection fraction and a reduction in end-systolic volume. This improvement was not caused by a reduction in infarct size. In addition, tracking of cp-MSCs transduced with luciferase revealed that cells remained in the heart for 4 days after the first injection but that the survival period was reduced after the second and third injections. Quantitative reverse transcription-polymerase chain reaction revealed similar expression of genes involved in the insulin signaling pathway when comparing cell-treated and placebo groups.
  
  
  CONCLUSIONS
  Improvement of cardiac function by cp-MSCs did not require permanent engraftment and was not mediated by the insulin signaling pathway.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. jpassipieri@hotmail.com.|Instituto Nacional de Cardiologia, Rua das Laranjeiras 374, Rio de Janeiro, 22240-006, Brazil. jpassipieri@hotmail.com.
authors.forename: Juliana A
authors.initials: JA
authors.lastname: Passipieri
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. kasaitais@yahoo.com.br.|Instituto Nacional de Cardiologia, Rua das Laranjeiras 374, Rio de Janeiro, 22240-006, Brazil. kasaitais@yahoo.com.br.
authors.forename: Tais H
authors.initials: TH
authors.lastname: Kasai-Brunswick
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. grazisuhett@gmail.com.|Departamento de Radiologia, Hospital Universitário Clementino Fraga Filho, Rua Rodolpho Paulo Rocco 255, Rio de Janeiro, 21941-913, Brazil. grazisuhett@gmail.com.
authors.forename: Grazielle
authors.initials: G
authors.lastname: Suhett
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. andrezab@biof.ufrj.br.|Instituto Nacional de Cardiologia, Rua das Laranjeiras 374, Rio de Janeiro, 22240-006, Brazil. andrezab@biof.ufrj.br.
authors.forename: Andreza B
authors.initials: AB
authors.lastname: Martins
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. guilhermevb@gmail.com.
authors.forename: Guilherme V
authors.initials: GV
authors.lastname: Brasil
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. camposbiomed@gmail.com.
authors.forename: Dilza B
authors.initials: DB
authors.lastname: Campos
authors.affiliation: Universidade Federal Fluminense, Rua Professor Hernani Melo 101, Niterói, 24210-130, Brazil. nn_rocha@hotmail.com.
authors.forename: Nazareth N
authors.initials: NN
authors.lastname: Rocha
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. isaliraa@hotmail.com.|Departamento de Radiologia, Hospital Universitário Clementino Fraga Filho, Rua Rodolpho Paulo Rocco 255, Rio de Janeiro, 21941-913, Brazil. isaliraa@hotmail.com.|Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Av Carlos Chagas Filho 373, Rio de Janeiro, 21941-902, Brazil. isaliraa@hotmail.com.
authors.forename: Isalira P
authors.initials: IP
authors.lastname: Ramos
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. debmello2003@gmail.com.
authors.forename: Debora B
authors.initials: DB
authors.lastname: Mello
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. deivid@biof.ufrj.br.
authors.forename: Deivid C
authors.initials: DC
authors.lastname: Rodrigues
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. beatrizchristie@yahoo.com.br.
authors.forename: Beatriz B
authors.initials: BB
authors.lastname: Christie
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. bjsm86@yahoo.com.br.
authors.forename: Bernardo J
authors.initials: BJ
authors.lastname: Silva-Mendes
authors.affiliation: Centro de Pesquisa, Tecnologia e Inovação, Universidade Veiga de Almeida, Rua Ibituruna 108, Rio de Janeiro, 20271-020, Brazil. balduinoa@uol.com.br.
authors.forename: Alex
authors.initials: A
authors.lastname: Balduíno
authors.affiliation: Centro Pré-Natal de Diagnóstico e Tratamento, Clínica Perinatal, Rua das Laranjeiras 445, Rio de Janeiro, 22240-002, Brazil. renato.sa@perinatal.com.br.
authors.forename: Renato M
authors.initials: RM
authors.lastname: Sá
authors.affiliation: Centro Pré-Natal de Diagnóstico e Tratamento, Clínica Perinatal, Rua das Laranjeiras 445, Rio de Janeiro, 22240-002, Brazil. laudelino.lopes@lhsc.on.ca.|Department of Obstetrics and Gynecology, Western University, London Health Sciences Centre-Victoria Hospital, B2-401, London, ON, N6H 5W9, Canada. laudelino.lopes@lhsc.on.ca.
authors.forename: Laudelino M
authors.initials: LM
authors.lastname: Lopes
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. rcoeli@biof.ufrj.br.|Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Av Carlos Chagas Filho 373, Rio de Janeiro, 21941-902, Brazil. rcoeli@biof.ufrj.br.
authors.forename: Regina C
authors.initials: RC
authors.lastname: Goldenberg
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. acarlos@biof.ufrj.br.|Instituto Nacional de Cardiologia, Rua das Laranjeiras 374, Rio de Janeiro, 22240-006, Brazil. acarlos@biof.ufrj.br.|Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Av Carlos Chagas Filho 373, Rio de Janeiro, 21941-902, Brazil. acarlos@biof.ufrj.br.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Campos de Carvalho
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho 373, Sala G2-053, Rio de Janeiro, RJ, 21941-902, Brazil. carvalhoab@biof.ufrj.br.|Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Av Carlos Chagas Filho 373, Rio de Janeiro, 21941-902, Brazil. carvalhoab@biof.ufrj.br.
authors.forename: Adriana B
authors.initials: AB
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D002306:Cardiac Volume; D002454:Cell Differentiation; D048430:Cell Shape; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007328:Insulin / Q000502:physiology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D010641:Phenotype; D015398:Signal Transduction; D013318:Stroke Volume
chemical_list: D007328:Insulin