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Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium
Author(s) -
PerezIlzarbe Maitane,
Agbulut Onnik,
Pelacho Beatriz,
Ciorba Cristina,
JoseEneriz Edurne San,
Desnos Michel,
Hagège Albert A.,
Aranda Pablo,
Andreu Enrique J.,
Menasché Philippe,
Prósper Felipe
Publication year - 2008
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2008.08.002
Subject(s) - paracrine signalling , myocyte , angiogenesis , microbiology and biotechnology , mmp9 , extracellular matrix , medicine , transplantation , mmp1 , myogenesis , mmp2 , cancer research , gene expression , biology , gene , downregulation and upregulation , biochemistry , cancer , metastasis , receptor
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. Methods and 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), antiapoptotics (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‐β, 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.