Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia model
Abstract Background Patients with critical limb ischemia (CLI) are at great risk of major amputation and cardiovascular events. Adipose-derived mesenchymal stem cell (ADSC) therapy is a promising therapeutic strategy for CLI, but the poor engraftment and insufficient angiogenic ability of ADSCs limi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Journal of Nanobiotechnology |
| Online Access: | https://doi.org/10.1186/s12951-022-01632-1 |
| _version_ | 1811265041592221696 |
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| author | Zekun Shen Weiyi Wang Jinxing Chen Bingyi Chen Yanan Tang Jiaxuan Hou Jiayan Li Shuang Liu Yifan Mei Liwei Zhang Shaoying Lu |
| author_facet | Zekun Shen Weiyi Wang Jinxing Chen Bingyi Chen Yanan Tang Jiaxuan Hou Jiayan Li Shuang Liu Yifan Mei Liwei Zhang Shaoying Lu |
| author_sort | Zekun Shen |
| collection | DOAJ |
| description | Abstract Background Patients with critical limb ischemia (CLI) are at great risk of major amputation and cardiovascular events. Adipose-derived mesenchymal stem cell (ADSC) therapy is a promising therapeutic strategy for CLI, but the poor engraftment and insufficient angiogenic ability of ADSCs limit their regenerative potential. Herein, we explored the potential of human umbilical vein endothelial cells (HUVECs)-derived small extracellular vesicles (sEVs) for enhancing the therapeutic efficacy of ADSCs in CLI. Results sEVs derived from hypoxic HUVECs enhanced the resistance of ADSCs to reactive oxygen species (ROS) and further improved the proangiogenic ability of ADSCs in vitro. We found that the hypoxic environment altered the composition of sEVs from HUVECs and that hypoxia increased the level of miR-486-5p in sEVs. Compared to normoxic sEVs (nsEVs), hypoxic sEVs (hsEVs) of HUVECs significantly downregulated the phosphatase and tensin homolog (PTEN) via direct targeting of miR-486-5p, therefore activating the AKT/MTOR/HIF-1α pathway and influencing the survival and pro-angiogenesis ability of ADSCs. In a hindlimb ischemia model, we discovered that hsEVs-primed ADSCs exhibited superior cell engraftment, and resulted in better angiogenesis and tissue repair. Conclusion hsEVs could be used as a therapeutic booster to improve the curative potential of ADSCs in a limb ischemia model. This finding offers new insight for CLI treatment. Graphical Abstract |
| first_indexed | 2024-04-12T20:15:24Z |
| format | Article |
| id | doaj.art-edbeaf7c584045ba9d22a88f2bc34910 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-12T20:15:24Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-edbeaf7c584045ba9d22a88f2bc349102022-12-22T03:18:09ZengBMCJournal of Nanobiotechnology1477-31552022-09-0120111910.1186/s12951-022-01632-1Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia modelZekun Shen0Weiyi Wang1Jinxing Chen2Bingyi Chen3Yanan Tang4Jiaxuan Hou5Jiayan Li6Shuang Liu7Yifan Mei8Liwei Zhang9Shaoying Lu10Department of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background Patients with critical limb ischemia (CLI) are at great risk of major amputation and cardiovascular events. Adipose-derived mesenchymal stem cell (ADSC) therapy is a promising therapeutic strategy for CLI, but the poor engraftment and insufficient angiogenic ability of ADSCs limit their regenerative potential. Herein, we explored the potential of human umbilical vein endothelial cells (HUVECs)-derived small extracellular vesicles (sEVs) for enhancing the therapeutic efficacy of ADSCs in CLI. Results sEVs derived from hypoxic HUVECs enhanced the resistance of ADSCs to reactive oxygen species (ROS) and further improved the proangiogenic ability of ADSCs in vitro. We found that the hypoxic environment altered the composition of sEVs from HUVECs and that hypoxia increased the level of miR-486-5p in sEVs. Compared to normoxic sEVs (nsEVs), hypoxic sEVs (hsEVs) of HUVECs significantly downregulated the phosphatase and tensin homolog (PTEN) via direct targeting of miR-486-5p, therefore activating the AKT/MTOR/HIF-1α pathway and influencing the survival and pro-angiogenesis ability of ADSCs. In a hindlimb ischemia model, we discovered that hsEVs-primed ADSCs exhibited superior cell engraftment, and resulted in better angiogenesis and tissue repair. Conclusion hsEVs could be used as a therapeutic booster to improve the curative potential of ADSCs in a limb ischemia model. This finding offers new insight for CLI treatment. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01632-1 |
| spellingShingle | Zekun Shen Weiyi Wang Jinxing Chen Bingyi Chen Yanan Tang Jiaxuan Hou Jiayan Li Shuang Liu Yifan Mei Liwei Zhang Shaoying Lu Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia model Journal of Nanobiotechnology |
| title | Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia model |
| title_full | Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia model |
| title_fullStr | Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia model |
| title_full_unstemmed | Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia model |
| title_short | Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia model |
| title_sort | small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose derived mesenchymal stem cells via mir 486 5p pten in a limb ischemia model |
| url | https://doi.org/10.1186/s12951-022-01632-1 |
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