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Cytotherapy. 2019 Apr;21(4):433-443. doi: 10.1016/j.jcyt.2018.12.007. Epub 2019 Mar 15.

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

Author information

1
Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, South Korea.
2
Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA. Electronic address: sbae30@emory.edu.
3
Department of Bioengineering, College of Engineering, Hanyang University, Seoul, South Korea.
4
Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, South Korea; Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: cdhlyj@yuhs.ac.

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.

KEYWORDS:

angiogenesis; flouresence-activated cell sorting enrichment; modified stem cell therapy; reperfusion

PMID:
30879964
DOI:
10.1016/j.jcyt.2018.12.007

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