Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia
Abstract Background Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficul...
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-021-02475-7 |
| _version_ | 1818576594350899200 |
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| author | Xing Zhang Yihong Jiang Qun Huang Zhaoyu Wu Hongji Pu Zhijue Xu Bo Li Xinwu Lu Xinrui Yang Jinbao Qin Zhiyou Peng |
| author_facet | Xing Zhang Yihong Jiang Qun Huang Zhaoyu Wu Hongji Pu Zhijue Xu Bo Li Xinwu Lu Xinrui Yang Jinbao Qin Zhiyou Peng |
| author_sort | Xing Zhang |
| collection | DOAJ |
| description | Abstract Background Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics. Methods ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted from ADSCs (G-ADSC-Exos) were isolated and characterized to coculture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high-glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson’s staining, immunofluorescence, and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored. Results The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high-glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel’s density than the ADSC-Exo and control groups by Masson’s staining and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1β, as well as the increased secretion of VEGF, IGF-1, and FGF. Conclusion Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia. |
| first_indexed | 2024-12-16T06:16:30Z |
| format | Article |
| id | doaj.art-e317719a11da488aa7ca5fe42fc06f9b |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-16T06:16:30Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj.art-e317719a11da488aa7ca5fe42fc06f9b2022-12-21T22:41:15ZengBMCStem Cell Research & Therapy1757-65122021-07-0112111310.1186/s13287-021-02475-7Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemiaXing Zhang0Yihong Jiang1Qun Huang2Zhaoyu Wu3Hongji Pu4Zhijue Xu5Bo Li6Xinwu Lu7Xinrui Yang8Jinbao Qin9Zhiyou Peng10Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineAbstract Background Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics. Methods ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted from ADSCs (G-ADSC-Exos) were isolated and characterized to coculture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high-glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson’s staining, immunofluorescence, and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored. Results The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high-glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel’s density than the ADSC-Exo and control groups by Masson’s staining and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1β, as well as the increased secretion of VEGF, IGF-1, and FGF. Conclusion Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia.https://doi.org/10.1186/s13287-021-02475-7Glyoxalase-1Adipose-derived stem cellsExosomesT2DMEndothelial cellsAngiogenesis |
| spellingShingle | Xing Zhang Yihong Jiang Qun Huang Zhaoyu Wu Hongji Pu Zhijue Xu Bo Li Xinwu Lu Xinrui Yang Jinbao Qin Zhiyou Peng Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia Stem Cell Research & Therapy Glyoxalase-1 Adipose-derived stem cells Exosomes T2DM Endothelial cells Angiogenesis |
| title | Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia |
| title_full | Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia |
| title_fullStr | Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia |
| title_full_unstemmed | Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia |
| title_short | Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia |
| title_sort | exosomes derived from adipose derived stem cells overexpressing glyoxalase 1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia |
| topic | Glyoxalase-1 Adipose-derived stem cells Exosomes T2DM Endothelial cells Angiogenesis |
| url | https://doi.org/10.1186/s13287-021-02475-7 |
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