title: Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium.
abstract: BACKGROUND
  The discrepancy between the functional improvements yielded experimentally by skeletal myoblasts (SM) transplanted in infarcted myocardium and the paucity of their long-term engraftment has raised the hypothesis of cell-mediated paracrine mechanisms.
  
  
  RESULTS
  We analyzed gene expression and growth factors released by undifferentiated human SM (CD56(+)), myotubes (SM cultured until confluence) and fibroblasts-like cells (CD56(-)). Gene expression revealed up-regulation of pro-angiogenic (PGF), anti-apoptotics (BAG-1, BCL-2), heart development (TNNT2, TNNC1) and extracellular matrix remodelling (MMP-2, MMP-7) genes in SM. In line with the gene expression profile, the analysis of culture supernatants of SM by ELISA identified the release of growth factors involved in angiogenesis (VEGF, PIGF, angiogenin, angiopoietin, HGF and PDGF-BB) as well as proteases involved in matrix remodelling (MMP2, MMP9 and MMP10) and their inhibitors (TIMPs). Culture of smooth muscle cells (SMC), cardiomyocytes (HL-1) and human umbilical vein endothelial cells (HUVECs) with SM-released conditioned media demonstrated an increased proliferation of HUVEC, SMC and cardiomyocytes (p<0.05) and a decrease in apoptosis of cardiomyocytes (p<0.05). Analysis of nude rats transplanted with human SM demonstrated expression of human-specific MMP-2, TNNI3, CNN3, PGF, TNNT2, PAX7, TGF-beta, and IGF-1 1 month after transplant.
  
  
  CONCLUSIONS
  Our data support the paracrine hypothesis whereby myoblast-secreted factors may contribute to the beneficial effects of myogenic cell transplantation in infarcted myocardium.
authors.affiliation: Hematology, Cardiology and Cell Therapy, Clínica Universitaria and Division of Cancer, Foundation for Applied Medical Research, Division of Cancer, University of Navarra, Pamplona, Spain.
authors.forename: Maitane
authors.initials: M
authors.lastname: Perez-Ilzarbe
authors.forename: Onnik
authors.initials: O
authors.lastname: Agbulut
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelacho
authors.forename: Cristina
authors.initials: C
authors.lastname: Ciorba
authors.forename: Edurne
authors.initials: E
authors.lastname: San Jose-Eneriz
authors.forename: Michel
authors.initials: M
authors.lastname: Desnos
authors.forename: Albert A
authors.initials: AA
authors.lastname: Hagège
authors.forename: Pablo
authors.initials: P
authors.lastname: Aranda
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Andreu
authors.forename: Philippe
authors.initials: P
authors.lastname: Menasché
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
mesh_terms: D000818:Animals; D017209:Apoptosis; D001706:Biopsy; D049109:Cell Proliferation; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D017261:Glycosylphosphatidylinositols; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D051381:Rats; D011923:Rats, Nude; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016896:Treatment Outcome; D019210:Troponin I / Q000096:biosynthesis / Q000235:genetics
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C098069:PIGF protein, human; C518658:TNNI2 protein, human; D014157:Transcription Factors; D019210:Troponin I; D012313:RNA; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2