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Allogeneic adipose stem cell therapy in acute myocardial infarction
Author(s) -
Rigol Montserrat,
Solanes Núria,
Roura Santiago,
Roqué Mercè,
Novensà Laura,
Dantas Ana Paula,
Martorell Jaume,
Sitges Marta,
Ramírez José,
BayésGenís Antoni,
Heras Magda
Publication year - 2014
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12195
Subject(s) - medicine , myocardial infarction , adipose tissue , ejection fraction , stem cell , mesenchymal stem cell , immune system , cardiology , cell therapy , stem cell therapy , heart failure , vascular endothelial growth factor , immunology , pathology , biology , vegf receptors , genetics
Background Stem cell therapy offers a promising approach to reduce the long‐term mortality rate associated with heart failure after acute myocardial infarction ( AMI ). To date, in vivo translational studies have not yet fully studied the immune response to allogeneic adipose tissue‐derived mesenchymal stem cells ( ATMSC s). We analysed the immune response and the histological and functional effects of allogeneic ATMSC s in a porcine model of reperfused AMI and determine the effect of administration timing. Design Pigs that survived AMI (24/26) received intracoronary administration of culture medium after reperfusion ( n = 6), ATMSC s after reperfusion ( n = 6), culture medium 7 days after AMI ( n = 6) or ATMSC s 7 days after AMI ( n = 6). At 3‐week follow‐up, cardiac function, alloantibodies and histological analysis were evaluated. Results Administration of ATMSC s after reperfusion and 7 days after AMI resulted in similar rates of cell engraftment; some of those cells expressed endothelial, smooth muscle and cardiomyogenic cell lineage markers. Delivery of ATMSC s after reperfusion compared with that performed at 7 days was more effective in increasing: vascular density (249 ± 64 vs. 161 ± 37 vessels/mm2; P < 0·01), T lymphocytes (1 ± 0·4 vs. 0·4 ± 0·3% of area CD 3 + ; P < 0·05) and expression of vascular endothelial growth factor ( VEGF ; 32 ± 7% vs. 20 ± 4% of area VEGF + ; P < 0·01). Allogeneic ATMSC ‐based therapy did not change ejection fraction but generated alloantibodies. Conclusions The present study is the first to demonstrate that allogeneic ATMSC s elicit an immune response and, when administered immediately after reperfusion, are more effective in increasing VEGF expression and neovascularization.