Enrichment of vascular endothelial growth factor secreting mesenchymal stromal cells enhances therapeutic angiogenesis in a mouse model of hind limb ischemia

Abstract Critical limb ischemia, a severe manifestation of peripheral artery disease, is emerging as a major concern in aging societies worldwide. Notably, cell-based gene therapy to induce angiogenesis in ischemic tissue has been investigated as treatment. Despite many studies demonstrating the eff...

Full description

Saved in:
Bibliographic Details
Published in:Cytotherapy (Oxford, England) England), 2019-04, Vol.21 (4), p.433-443
Main Authors: PARK, JIN SIL, BAE, SEONG-HO, JUNG, SUBIN, LEE, MINHYUNG, CHOI, DONGHOON
Format: Article
Language:English
Subjects:
Advanced Basic Science
angiogenesis
Animals
Disease Models, Animal
Fibrosis
flouresence-activated cell sorting enrichment
Gene Expression
Genetic Therapy
Hindlimb - blood supply
Hindlimb - pathology
Humans
Ischemia - pathology
Ischemia - therapy
Male
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells - metabolism
Mice, Inbred BALB C
Mice, Inbred C57BL
modified stem cell therapy
Necrosis
Neovascularization, Physiologic
Other
Perfusion
Plasmids - metabolism
Rats, Sprague-Dawley
reperfusion
Transfection
Vascular Endothelial Growth Factor A - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Critical limb ischemia, a severe manifestation of peripheral artery disease, is emerging as a major concern in aging societies worldwide. Notably, cell-based gene therapy to induce angiogenesis in ischemic tissue has been investigated as treatment. Despite many studies demonstrating the efficacy of this approach, better therapies are required to prevent serious sequelae such as claudication, amputation and other cardiovascular events. We have now established a simplified method to enhance the effects of therapeutic transgenes by selecting for and transplanting only transduced cells. Herein, mesenchymal stromal cells were transfected to co-express vascular endothelial growth factor as angiogenic factor and enhanced green fluorescent protein as marker. Transfected cells were then collected using flow cytometry based on green fluorescence and transplanted into ischemic hind limbs in mice. Compared with unsorted or untransfected cells, purified cells significantly improved blood perfusion within 21days, suggesting that transplanting only cells that overexpress vascular endothelial growth factor enhances therapeutic angiogenesis. Importantly, this approach may prove to be useful in cell-based gene therapy against a wide spectrum of diseases, simply by replacing the gene to be delivered or the cell to be transplanted.
ISSN:1465-3249
1477-2566
DOI:10.1016/j.jcyt.2018.12.007