Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis
The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological proc...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Drug Delivery |
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| Online Access: | http://dx.doi.org/10.1080/10717544.2021.2023699 |
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| author | Chengqi Yan Jing Chen Cheng Wang Meng Yuan Yu Kang Zihan Wu Wenqing Li Guolei Zhang Hans-Günther Machens Yuval Rinkevich Zhenbing Chen Xiaofan Yang Xiang Xu |
| author_facet | Chengqi Yan Jing Chen Cheng Wang Meng Yuan Yu Kang Zihan Wu Wenqing Li Guolei Zhang Hans-Günther Machens Yuval Rinkevich Zhenbing Chen Xiaofan Yang Xiang Xu |
| author_sort | Chengqi Yan |
| collection | DOAJ |
| description | The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions in vitro, together with the promotion of angiogenesis and enhanced diabetic wound healing in vivo. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs. |
| first_indexed | 2024-12-20T06:37:20Z |
| format | Article |
| id | doaj.art-be633668f12c4ff09bec236f94e89765 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-20T06:37:20Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-be633668f12c4ff09bec236f94e897652022-12-21T19:49:58ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642022-12-0129121422810.1080/10717544.2021.20236992023699Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesisChengqi Yan0Jing Chen1Cheng Wang2Meng Yuan3Yu Kang4Zihan Wu5Wenqing Li6Guolei Zhang7Hans-Günther Machens8Yuval Rinkevich9Zhenbing Chen10Xiaofan Yang11Xiang Xu12Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hand and Foot Surgery, Huazhong University of Science and Technology, Union Shenzhen HospitalDepartment of Hand and Foot Surgery, Huazhong University of Science and Technology, Union Shenzhen HospitalDepartment of Plastic and Hand Surgery, Technical University of MunichInstitute of Lung Biology and Disease, Helmholtz Zentrum MünchenDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions in vitro, together with the promotion of angiogenesis and enhanced diabetic wound healing in vivo. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs.http://dx.doi.org/10.1080/10717544.2021.2023699milk-derived exosomesmir-31-5pdrug deliverydiabetic woundangiogenesis |
| spellingShingle | Chengqi Yan Jing Chen Cheng Wang Meng Yuan Yu Kang Zihan Wu Wenqing Li Guolei Zhang Hans-Günther Machens Yuval Rinkevich Zhenbing Chen Xiaofan Yang Xiang Xu Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis Drug Delivery milk-derived exosomes mir-31-5p drug delivery diabetic wound angiogenesis |
| title | Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis |
| title_full | Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis |
| title_fullStr | Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis |
| title_full_unstemmed | Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis |
| title_short | Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis |
| title_sort | milk exosomes mediated mir 31 5p delivery accelerates diabetic wound healing through promoting angiogenesis |
| topic | milk-derived exosomes mir-31-5p drug delivery diabetic wound angiogenesis |
| url | http://dx.doi.org/10.1080/10717544.2021.2023699 |
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