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 (2018). Myocardial infarction stabilization by cell-based expression of controlled Vascular Endothelial Growth Factor levels. Journal of Cellular and Molecular Medicine, 22(5), pp. 2580-2591. Wiley 10.1111/jcmm.13511

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiovascular Surgery

UniBE Contributor:

Cook, Stéphane and Carrel, Thierry

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1582-1838

Publisher:

Wiley

Language:

English

Submitter:

Daniela Huber

Date Deposited:

24 Apr 2018 15:28

Last Modified:

24 Apr 2018 15:28

Publisher DOI:

10.1111/jcmm.13511

PubMed ID:

29478261

Uncontrolled Keywords:

Vascular Endothelial Growth Factor adipose stem cells angiogenesis cell therapy myocardial infarction

BORIS DOI:

10.7892/boris.114609

URI:

https://boris.unibe.ch/id/eprint/114609

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