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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Cell+Mol+Med
2018 ; 22
(5
): 2580-2591
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Myocardial infarction stabilization by cell-based expression of controlled
Vascular Endothelial Growth Factor levels
#MMPMID29478261
Melly L
; Cerino G
; Frobert A
; Cook S
; Giraud MN
; Carrel T
; Tevaearai Stahel HT
; Eckstein F
; Rondelet B
; Marsano A
; Banfi A
J Cell Mol Med
2018[May]; 22
(5
): 2580-2591
PMID29478261
show ga
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.