Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels. Issue 5 (25th February 2018)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of cellular and molecular medicine. Volume 22:Issue 5(2018)
• Page Start: 2580
• Page End: 2591
• Publication Date: 2018-02-25
• Subjects: myocardial infarction -- adipose stem cells -- Vascular Endothelial Growth Factor -- angiogenesis -- cell therapy; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.13511
• Languages: English
• ISSNs: 1582-1838

Abstract

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.