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...

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Bibliographic Details
Published inDrug delivery Vol. 29; no. 1; pp. 214 - 228
Main Authors Yan, Chengqi, Chen, Jing, Wang, Cheng, Yuan, Meng, Kang, Yu, Wu, Zihan, Li, Wenqing, Zhang, Guolei, Machens, Hans-Günther, Rinkevich, Yuval, Chen, Zhenbing, Yang, Xiaofan, Xu, Xiang
Format Journal Article
LanguageEnglish
Published England Taylor & Francis 01.12.2022
Taylor & Francis Ltd
Taylor & Francis Group
Subjects
Angiogenesis
Animals
Diabetes
Diabetes Mellitus, Experimental - complications
diabetic wound
Drug Carriers - metabolism
drug delivery
Exosomes - metabolism
Gene expression
Human Umbilical Vein Endothelial Cells
Humans
Male
Mice
Mice, Inbred BALB C
MicroRNAs
MicroRNAs - administration & dosage
MicroRNAs - pharmacology
Milk
Milk-derived exosomes
miR-31-5p
Neovascularization, Physiologic - drug effects
Wound healing
Wound Healing - drug effects
Wounds and Injuries - etiology
Wounds and Injuries - pathology
diabetic wound
drug delivery
angiogenesis
Milk-derived exosomes
miR-31-5p
Online AccessGet full text

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Abstract 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.
AbstractList 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.
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.
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.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.
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 , together with the promotion of angiogenesis and enhanced diabetic wound healing . 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.
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.
Author Yuan, Meng
Li, Wenqing
Yan, Chengqi
Wu, Zihan
Rinkevich, Yuval
Yang, Xiaofan
Zhang, Guolei
Chen, Zhenbing
Machens, Hans-Günther
Kang, Yu
Wang, Cheng
Xu, Xiang
Chen, Jing
Author_xml – sequence: 1
  givenname: Chengqi
  surname: Yan
  fullname: Yan, Chengqi
  organization: Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
– sequence: 2
  givenname: Jing
  surname: Chen
  fullname: Chen, Jing
  organization: Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
– sequence: 3
  givenname: Cheng
  surname: Wang
  fullname: Wang, Cheng
  organization: Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
– sequence: 4
  givenname: Meng
  surname: Yuan
  fullname: Yuan, Meng
  organization: Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
– sequence: 5
  givenname: Yu
  surname: Kang
  fullname: Kang, Yu
  organization: Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
– sequence: 6
  givenname: Zihan
  surname: Wu
  fullname: Wu, Zihan
  organization: Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
– sequence: 7
  givenname: Wenqing
  surname: Li
  fullname: Li, Wenqing
  organization: Department of Hand and Foot Surgery, Huazhong University of Science and Technology, Union Shenzhen Hospital
– sequence: 8
  givenname: Guolei
  surname: Zhang
  fullname: Zhang, Guolei
  organization: Department of Hand and Foot Surgery, Huazhong University of Science and Technology, Union Shenzhen Hospital
– sequence: 9
  givenname: Hans-Günther
  surname: Machens
  fullname: Machens, Hans-Günther
  organization: Department of Plastic and Hand Surgery, Technical University of Munich
– sequence: 10
  givenname: Yuval
  surname: Rinkevich
  fullname: Rinkevich, Yuval
  organization: Institute of Regenerative Biology and Medicine, Helmholtz Zentrum München
– sequence: 11
  givenname: Zhenbing
  surname: Chen
  fullname: Chen, Zhenbing
  organization: Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
– sequence: 12
  givenname: Xiaofan
  surname: Yang
  fullname: Yang, Xiaofan
  organization: Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
– sequence: 13
  givenname: Xiang
  surname: Xu
  fullname: Xu, Xiang
  organization: Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34985397$$D View this record in MEDLINE/PubMed
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Copyright 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2022
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Keywords diabetic wound
drug delivery
angiogenesis
Milk-derived exosomes
miR-31-5p
Language English
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Snippet The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound...
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StartPage 214
SubjectTerms Angiogenesis
Animals
Diabetes
Diabetes Mellitus, Experimental - complications
diabetic wound
Drug Carriers - metabolism
drug delivery
Exosomes - metabolism
Gene expression
Human Umbilical Vein Endothelial Cells
Humans
Male
Mice
Mice, Inbred BALB C
MicroRNAs
MicroRNAs - administration & dosage
MicroRNAs - pharmacology
Milk
Milk-derived exosomes
miR-31-5p
Neovascularization, Physiologic - drug effects
Wound healing
Wound Healing - drug effects
Wounds and Injuries - etiology
Wounds and Injuries - pathology
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Title Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis
URI https://www.tandfonline.com/doi/abs/10.1080/10717544.2021.2023699
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