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Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels

Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)‐based technique to rapidly purify transdu...

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Autores principales: Melly, Ludovic, Cerino, Giulia, Frobert, Aurélien, Cook, Stéphane, Giraud, Marie‐Noëlle, Carrel, Thierry, Tevaearai Stahel, Hendrik T., Eckstein, Friedrich, Rondelet, Benoît, Marsano, Anna, Banfi, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908097/
https://www.ncbi.nlm.nih.gov/pubmed/29478261
http://dx.doi.org/10.1111/jcmm.13511
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author Melly, Ludovic
Cerino, Giulia
Frobert, Aurélien
Cook, Stéphane
Giraud, Marie‐Noëlle
Carrel, Thierry
Tevaearai Stahel, Hendrik T.
Eckstein, Friedrich
Rondelet, Benoît
Marsano, Anna
Banfi, Andrea
author_facet Melly, Ludovic
Cerino, Giulia
Frobert, Aurélien
Cook, Stéphane
Giraud, Marie‐Noëlle
Carrel, Thierry
Tevaearai Stahel, Hendrik T.
Eckstein, Friedrich
Rondelet, Benoît
Marsano, Anna
Banfi, Andrea
author_sort Melly, Ludovic
collection PubMed
description Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)‐based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell‐based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF‐expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS‐purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia.
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spelling pubmed-59080972018-05-03 Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels Melly, Ludovic Cerino, Giulia Frobert, Aurélien Cook, Stéphane Giraud, Marie‐Noëlle Carrel, Thierry Tevaearai Stahel, Hendrik T. Eckstein, Friedrich Rondelet, Benoît Marsano, Anna Banfi, Andrea J Cell Mol Med Original Articles Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)‐based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell‐based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF‐expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS‐purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia. John Wiley and Sons Inc. 2018-02-25 2018-05 /pmc/articles/PMC5908097/ /pubmed/29478261 http://dx.doi.org/10.1111/jcmm.13511 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Melly, Ludovic
Cerino, Giulia
Frobert, Aurélien
Cook, Stéphane
Giraud, Marie‐Noëlle
Carrel, Thierry
Tevaearai Stahel, Hendrik T.
Eckstein, Friedrich
Rondelet, Benoît
Marsano, Anna
Banfi, Andrea
Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels
title Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels
title_full Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels
title_fullStr Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels
title_full_unstemmed Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels
title_short Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels
title_sort myocardial infarction stabilization by cell‐based expression of controlled vascular endothelial growth factor levels
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908097/
https://www.ncbi.nlm.nih.gov/pubmed/29478261
http://dx.doi.org/10.1111/jcmm.13511
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