Abstract | BACKGROUND: Even though mesenchymal stem cells (MSCs) have angiogenic property, their cytokine secretory capacity is limited to treat ischemic vascular disorders. In present study, we produced genome-edited MSCs that secreted dual chemokine granulocyte chemotactic protein-2 (GCP-2) and stromal-derived factor-1α (SDF-1α) and determined their therapeutic potential in the context of experimental ischemia. METHODS: GCP-2 and SDF-1α genes were integrated into safe harbor site at the safe harbor genomic locus of amniotic mesenchymal stem cells (AMM) via transcription activator-like effector nucleases ( TALEN). GCP-2 and SDF-1α gene-edited AMM (AMM/GS) were used for quantitative (q)-PCR, Matrigel tube formation, cell migration, Matrigel plug assays and in vivo therapeutic assays using hindlimb ischemia mouse model. RESULTS: AMM/GS-derived culture media (CM) induced significantly higher tube lengths and branching points as compared to AMM/S CM and AMM CM. Interestingly, Matrigel plug assays revealed that significantly higher levels of red blood cells were found in AMM/GS than AMM/S and AMM Matigel plugs and exhibited micro-vascular like formation. Cells was transplanted into ischemic mouse hindlimbs and compared with control groups. AMM/GS injection prevented limb loss and augmented blood perfusion, suggesting that enhances neovascularization in hindlimb ischemia. In addition, transplanted AMM/GS revealed high vasculogenic potential in vivo compared with transplanted AMM/S. CONCLUSION: Taken together, genome-edited MSCs that express dual chemokine GCP-2 and SDF-1α might be alternative therapeutic options for the treatment of ischemic vascular disease.
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Authors | In Sil Jeong, Youngjin Park, Hyun Aae Ryu, Hyun Sook An, Ju Hye Han, Sung-Whan Kim |
Journal | International journal of cardiology
(Int J Cardiol)
Vol. 260
Pg. 156-162
(06 01 2018)
ISSN: 1874-1754 [Electronic] Netherlands |
PMID | 29506937
(Publication Type: Journal Article)
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Copyright | Copyright © 2018 Elsevier B.V. All rights reserved. |
Chemical References |
- Transcription Activator-Like Effector Nucleases
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Topics |
- Amnion
(cytology, physiology)
- Animals
- Chemotaxis
(physiology)
- Gene Editing
(methods)
- Human Umbilical Vein Endothelial Cells
(physiology)
- Humans
- Ischemia
(pathology, therapy)
- Male
- Mesenchymal Stem Cell Transplantation
(methods)
- Mesenchymal Stem Cells
(metabolism, physiology)
- Mice
- Mice, Nude
- Neovascularization, Physiologic
(physiology)
- Transcription Activator-Like Effector Nucleases
(physiology)
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