Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783315656686436352 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5908097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT mellyludovic myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT cerinogiulia myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT frobertaurelien myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT cookstephane myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT giraudmarienoelle myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT carrelthierry myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT tevaearaistahelhendrikt myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT ecksteinfriedrich myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT rondeletbenoit myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT marsanoanna myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels AT banfiandrea myocardialinfarctionstabilizationbycellbasedexpressionofcontrolledvascularendothelialgrowthfactorlevels |