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Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling

In the post-infarcted heart, grafting of precursor cells may partially restore heart function but the improvement is modest and the mechanisms involved remain to be elucidated. Here, we explored this issue by transplanting C2C12 myoblasts, genetically engineered to express enhanced green fluorescent...

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Autores principales: Formigli, Lucia, Perna, Avio-Maria, Meacci, Elisabetta, Cinci, Lorenzo, Margheri, Martina, Nistri, Silvia, Tani, Alessia, Silvertown, Josh, Orlandini, Giovanni, Porciani, Cristina, Zecchi-Orlandini, Sandra, Medin, Jeffrey, Bani, Daniele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401276/
https://www.ncbi.nlm.nih.gov/pubmed/17979884
http://dx.doi.org/10.1111/j.1582-4934.2007.00111.x
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author Formigli, Lucia
Perna, Avio-Maria
Meacci, Elisabetta
Cinci, Lorenzo
Margheri, Martina
Nistri, Silvia
Tani, Alessia
Silvertown, Josh
Orlandini, Giovanni
Porciani, Cristina
Zecchi-Orlandini, Sandra
Medin, Jeffrey
Bani, Daniele
author_facet Formigli, Lucia
Perna, Avio-Maria
Meacci, Elisabetta
Cinci, Lorenzo
Margheri, Martina
Nistri, Silvia
Tani, Alessia
Silvertown, Josh
Orlandini, Giovanni
Porciani, Cristina
Zecchi-Orlandini, Sandra
Medin, Jeffrey
Bani, Daniele
author_sort Formigli, Lucia
collection PubMed
description In the post-infarcted heart, grafting of precursor cells may partially restore heart function but the improvement is modest and the mechanisms involved remain to be elucidated. Here, we explored this issue by transplanting C2C12 myoblasts, genetically engineered to express enhanced green fluorescent protein (eGFP) or eGFP and the cardiotropic hormone relaxin (RLX) through coronary venous route to swine with experimental chronic myocardial infarction. The rationale was to deliver constant, biologically effective levels of RLX at the site of cell engraftment. One month after engraftment, histological analysis showed that C2C12 myoblasts selectively settled in the ischaemic scar and were located around blood vessels showing an activated endothelium (ICAM-1-,VCAM-positive). C2C12 myoblasts did not trans-differentiate towards a cardiac phenotype, but did induce extracellular matrix remodelling by the secretion of matrix metalloproteases (MMP) and increase microvessel density through the expression of vascular endothelial growth factor (VEGF). Relaxin-producing C2C12 myoblasts displayed greater efficacy to engraft the post-ischaemic scar and to induce extracellular matrix re-modelling and angiogenesis as compared with the control cells. By echocardio-graphy, C2C12-engrafted swine showed improved heart contractility compared with the ungrafted controls, especially those producing RLX. We suggest that the beneficial effects of myoblast grafting on cardiac function are primarily dependent on the paracrine effects of transplanted cells on extracellular matrix remodelling and vascularization. The combined treatment with myoblast transplantation and local RLX production may be helpful in preventing deleterious cardiac remodelling and may hold therapeutic possibility for post-infarcted patients.
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spelling pubmed-44012762015-04-27 Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling Formigli, Lucia Perna, Avio-Maria Meacci, Elisabetta Cinci, Lorenzo Margheri, Martina Nistri, Silvia Tani, Alessia Silvertown, Josh Orlandini, Giovanni Porciani, Cristina Zecchi-Orlandini, Sandra Medin, Jeffrey Bani, Daniele J Cell Mol Med In Focus In the post-infarcted heart, grafting of precursor cells may partially restore heart function but the improvement is modest and the mechanisms involved remain to be elucidated. Here, we explored this issue by transplanting C2C12 myoblasts, genetically engineered to express enhanced green fluorescent protein (eGFP) or eGFP and the cardiotropic hormone relaxin (RLX) through coronary venous route to swine with experimental chronic myocardial infarction. The rationale was to deliver constant, biologically effective levels of RLX at the site of cell engraftment. One month after engraftment, histological analysis showed that C2C12 myoblasts selectively settled in the ischaemic scar and were located around blood vessels showing an activated endothelium (ICAM-1-,VCAM-positive). C2C12 myoblasts did not trans-differentiate towards a cardiac phenotype, but did induce extracellular matrix remodelling by the secretion of matrix metalloproteases (MMP) and increase microvessel density through the expression of vascular endothelial growth factor (VEGF). Relaxin-producing C2C12 myoblasts displayed greater efficacy to engraft the post-ischaemic scar and to induce extracellular matrix re-modelling and angiogenesis as compared with the control cells. By echocardio-graphy, C2C12-engrafted swine showed improved heart contractility compared with the ungrafted controls, especially those producing RLX. We suggest that the beneficial effects of myoblast grafting on cardiac function are primarily dependent on the paracrine effects of transplanted cells on extracellular matrix remodelling and vascularization. The combined treatment with myoblast transplantation and local RLX production may be helpful in preventing deleterious cardiac remodelling and may hold therapeutic possibility for post-infarcted patients. Blackwell Publishing Ltd 2007-09 2007-08-31 /pmc/articles/PMC4401276/ /pubmed/17979884 http://dx.doi.org/10.1111/j.1582-4934.2007.00111.x Text en
spellingShingle In Focus
Formigli, Lucia
Perna, Avio-Maria
Meacci, Elisabetta
Cinci, Lorenzo
Margheri, Martina
Nistri, Silvia
Tani, Alessia
Silvertown, Josh
Orlandini, Giovanni
Porciani, Cristina
Zecchi-Orlandini, Sandra
Medin, Jeffrey
Bani, Daniele
Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling
title Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling
title_full Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling
title_fullStr Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling
title_full_unstemmed Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling
title_short Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling
title_sort paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling
topic In Focus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401276/
https://www.ncbi.nlm.nih.gov/pubmed/17979884
http://dx.doi.org/10.1111/j.1582-4934.2007.00111.x
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