Open AccessMyocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels
Author(s) -
Melly Ludovic,
Cerino Giulia,
Frobert Aurélien,
Cook Stéphane,
Giraud MarieNoëlle,
Carrel Thierry,
Tevaearai Stahel Hendrik T.,
Eckstein Friedrich,
Rondelet Benoît,
Marsano Anna,
Banfi Andrea
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13511
Subject(s) - angiogenesis , stromal cell , population , progenitor cell , vascular endothelial growth factor , arteriogenesis , medicine , myocardial infarction , cell sorting , endothelial progenitor cell , stromal vascular fraction , cell , immunology , cancer research , biology , stem cell , microbiology and biotechnology , flow cytometry , vegf receptors , genetics , environmental health
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.