Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium

被引：105

作者：

Perez-Ilzarbe, Maitane ^{[1
,2
]}

Agbulut, Onnik ^{[3
]}

Pelacho, Beatriz ^{[1
,2
]}

Ciorba, Cristina ^{[1
,2
]}

Jose-Eneriz, Edume San ^{[1
,2
]}

Desnos, Michel ^{[4
,5
,6
]}

Hagege, Albert A. ^{[4
,5
,7
]}

Aranda, Pablo ^{[1
,2
]}

Andreu, Enrique J. ^{[1
,2
]}

Menasche, Philippe ^{[3
]}

Prosper, Felipe ^{[1
,2
]}

机构：

[1] Univ Navarra, Fdn Appl Med Res, Div Canc, E-31080 Pamplona, Spain

[2] Clin Univ, Pamplona 31008, Spain

[3] Univ Paris 07, Dept Biochem, EA 300, Paris, France

[4] Univ Paris 05, Fac Med, Paris, France

[5] INSERM, U633, Paris, France

[6] Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, Paris, France

[7] Hop Europeen Georges Pompidou, AP HP, Dept Cardiovasc Surg, Paris, France

来源：

EUROPEAN JOURNAL OF HEART FAILURE | 2008年 / 10卷 / 11期

关键词：

Skeletal myoblast; Paracrine; Cell therapy; Myocardial infarction;

D O I：

10.1016/j.ejheart.2008.08.002

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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-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. (C) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

引用

页码：1065 / 1072

页数：8

共 47 条

[1] Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium [J].

Agbulut, O ;

Vandervelde, S ;

Al Attar, N ;

Larghero, J ;

Ghostine, S ;

Léobon, B ;

Robidel, E ;

Borsani, P ;

Le Lorc'h, M ;

Bissery, A ;

Chomienne, C ;

Bruneval, P ;

Marolleau, JP ;

Vilquin, JT ;

Hagège, A ;

Samuel, JL ;

Menasché, P .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2004, 44 (02) :458-463

[2] Cellular, but not direct, adenoviral delivery of vascular endothelial growth factor results in improved left ventricular function and neovascularization in dilated ischemic cardiomyopathy [J].

Askari, A ;

Unzek, S ;

Goldman, CK ;

Ellis, SG ;

Thomas, JD ;

DiCorleto, PE ;

Topol, EJ ;

Penn, MS .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2004, 43 (10) :1908-1914

[3] Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium [J].

Balsam, LB ;

Wagers, AJ ;

Christensen, JL ;

Kofidis, T ;

Weissman, IL ;

Robbins, RC .

NATURE, 2004, 428 (6983) :668-673

[4] Mapping TNNC1, the gene that encodes cardiac troponin I in the human and the mouse [J].

Bermingham, N ;

Hernandez, D ;

Balfour, A ;

Gilmour, F ;

Martin, JE ;

Fisher, EMC .

GENOMICS, 1995, 30 (03) :620-622

[5] Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat [J].

Boixel, C ;

Fontaine, V ;

Rücker-Martin, C ;

Milliez, P ;

Louedec, L ;

Michel, JB ;

Jacob, MP ;

Hatem, SN .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2003, 42 (02) :336-344

[6] Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells reduces infarct size and apoptosis and improves cardiac function in chronic ischemic heart failure [J].

Bonaros, Nikolaos ;

Rauf, Rauend ;

Wolf, Dominik ;

Margreiter, Eva ;

Tzankov, Alexandar ;

Schlechta, Bernhard ;

Kocher, Alfred ;

Ott, Harald ;

Schachner, Thomas ;

Hering, Steffen ;

Bonatti, Johannes ;

Laufer, Guenther .

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2006, 132 (06) :1321-U13

[7]

Brocheriou V, 2000, J GENE MED, V2, P326, DOI 10.1002/1521-2254(200009/10)2:5<326::AID-JGM133>3.0.CO

[8]

2-1

[9] Expression of endothelial nitric oxide synthase in the vascular wall during arteriogenesis [J].

Cai, WJ ;

Kocsis, E ;

Luo, XG ;

Schaper, W ;

Schaper, J .

MOLECULAR AND CELLULAR BIOCHEMISTRY, 2004, 264 (1-2) :193-200

[10] Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions [J].

Carmeliet, P ;

Moons, L ;

Luttun, A ;

Vincenti, V ;

Compernolle, V ;

De Mol, M ;

Wu, Y ;

Bon, F ;

Devy, L ;

Beck, H ;

Scholz, D ;

Acker, T ;

DiPalma, T ;

Dewerchin, M ;

Noel, A ;

Stalmans, I ;

Barra, A ;

Blacher, S ;

Vandendriessche, T ;

Ponten, A ;

Eriksson, U ;

Plate, KH ;

Foidart, JM ;

Schaper, W ;

Charnock-Jones, DS ;

Hicklin, DJ ;

Herbert, JM ;

Collen, D ;

Persico, MG .

NATURE MEDICINE, 2001, 7 (05) :575-583

← 1 2 3 4 5 →