Myocardial infarction stabilization by cell-based expression of controlled Vascular Endothelial Growth Factor levels.
Publisher DOI
PubMed ID
29478261
Abstract
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.
Date Issued
2018-05
Publication Type
Article
Subject(s)
Subjects
Vascular Endothelial Growth Factor adipose stem cells angiogenesis cell therapy myocardial infarction
Language(s)
en
Author(s)
Melly, Ludovic | |
Cerino, Giulia | |
Frobert, Aurélien | |
Giraud, Marie-Noëlle | |
Tevaearai Stahel, Hendrik T | |
Eckstein, Friedrich | |
Rondelet, Benoît | |
Marsano, Anna | |
Banfi, Andrea |
Journal
Journal of Cellular and Molecular Medicine
Publisher
Wiley
ISSN
1582-1838
Access(Rights)
open.access