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


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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.

Original languageEnglish
Pages (from-to)433-443
Number of pages11
Issue number4
Publication statusPublished - 2019 Apr

Bibliographical note

Funding Information:
This research was supported by a grant from the Korea Healthcare Technology Research & Development Project, Ministry for Health & Welfare, Republic of Korea (numbers A085136 and HI15C1277 ), the Mid-Career Researcher Program through an national research foundation of korea (NRF) grant funded by the ministry of education, science and technology (MEST), Republic of Korea (number 2015R1A2A2A01002731 ), the Bio & Medical Technology Development Program of the NRF funded by Korean government, ministry of science, ICT and future planning (MSIP) 2015M3A9C6031514 and the Cardiovascular Research Center, Seoul, Korea.

Publisher Copyright:
© 2019 International Society for Cell and Gene Therapy

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research


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