Serum exosomes accelerate diabetic wound healing by promoting angiogenesis and ECM formation

doi:10.1002/cbin.11627

. 2021 Sep;45(9):1976-1985.

doi: 10.1002/cbin.11627. Epub 2021 Jun 3.

Serum exosomes accelerate diabetic wound healing by promoting angiogenesis and ECM formation

Liushan Chen¹, Linghao Qin², Chujun Chen¹, Qiong Hu¹, Junjian Wang³, Juan Shen¹

Affiliations

¹ Department of Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
² School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
³ National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.

PMID: 33991016
DOI: 10.1002/cbin.11627

Serum exosomes accelerate diabetic wound healing by promoting angiogenesis and ECM formation

Liushan Chen et al. Cell Biol Int. 2021 Sep.

. 2021 Sep;45(9):1976-1985.

doi: 10.1002/cbin.11627. Epub 2021 Jun 3.

Authors

Liushan Chen¹, Linghao Qin², Chujun Chen¹, Qiong Hu¹, Junjian Wang³, Juan Shen¹

Affiliations

¹ Department of Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
² School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
³ National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.

PMID: 33991016
DOI: 10.1002/cbin.11627

Abstract

Nonhealing wounds in diabetes remain a global clinical and research challenge. Exosomes are primary mediators of cell paracrine action, which are shown to promote tissue repair and regeneration. In this study, we investigated the effects of serum derived exosomes (Serum-Exos) on diabetic wound healing and its possible mechanisms. Serum-Exos were isolated from blood serum of normal healthy mice and identified by transmission electron microscopy and western blot. The effects of Serum-Exos on diabetic wound healing, fibroblast growth and migration, angiogenesis and extracellular matrix (ECM) formation were investigated. Our results showed that the isolated Serum-Exos exhibited a sphere-shaped morphology with a mean diameter at 150 nm, and expressed classical markers of exosomes including HSP70, TSG101, and CD63. Treatment with Serum-Exos elevated the percentage of wound closure and shortened the time of healing in diabetic mice. Mechanistically, Serum-Exos promoted granulation tissue formation and increased the expression of CD31, fibronectin and collagen-ɑ in diabetic mice. Serum-Exos also promoted the migration of NIH/3T3 cells, which was associated with increased expression levels of PCNA, Ki67, collagen-α and fibronectin. In addition, Serum-Exos enhanced tube formation in human umbilical vein endothelial cells and induced the expression of CD31 at both protein and messenger RNA levels. Collectively, our results suggest that Serum-Exos may facilitate the wound healing in diabetic mice by promoting angiogenesis and ECM formation, and show the potential application in treating diabetic wounds.

Keywords: angiogenesis; diabetic healing; extracellular matrix; migration; serum exosomes.

PubMed Disclaimer

Cited by

Therapeutic application of mesenchymal stem cell-derived exosomes in skin wound healing.
Sun Y, Zhang S, Shen Y, Lu H, Zhao X, Wang X, Wang Y, Wang T, Liu B, Yao L, Wen J. Sun Y, et al. Front Bioeng Biotechnol. 2024 Aug 5;12:1428793. doi: 10.3389/fbioe.2024.1428793. eCollection 2024. Front Bioeng Biotechnol. 2024. PMID: 39161350 Free PMC article. Review.
In Vitro and In Vivo Evaluation of Epidermal Growth Factor (EGF) Loaded Alginate-Hyaluronic Acid (AlgHA) Microbeads System for Wound Healing.
Ali M, Kwak SH, Byeon JY, Choi HJ. Ali M, et al. J Funct Biomater. 2023 Jul 28;14(8):403. doi: 10.3390/jfb14080403. J Funct Biomater. 2023. PMID: 37623648 Free PMC article.
Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing.
Littig JPB, Moellmer R, Agrawal DK, Rai V. Littig JPB, et al. World J Diabetes. 2023 Jan 15;14(1):35-47. doi: 10.4239/wjd.v14.i1.35. World J Diabetes. 2023. PMID: 36684384 Free PMC article. Review.
microRNAs delivered by small extracellular vesicles in MSCs as an emerging tool for bone regeneration.
Liu R, Wu S, Liu W, Wang L, Dong M, Niu W. Liu R, et al. Front Bioeng Biotechnol. 2023 Aug 31;11:1249860. doi: 10.3389/fbioe.2023.1249860. eCollection 2023. Front Bioeng Biotechnol. 2023. PMID: 37720323 Free PMC article. Review.
Exosomes Derived from Mouse Breast Carcinoma Cells Facilitate Diabetic Wound Healing.
Zhang C, Xiao W, Wang H, Li L, Yang Y, Hao Y, Xu Z, Chen H, Nan W. Zhang C, et al. Tissue Eng Regen Med. 2024 Jun;21(4):571-586. doi: 10.1007/s13770-024-00629-1. Epub 2024 Mar 12. Tissue Eng Regen Med. 2024. PMID: 38472732 Free PMC article.

See all "Cited by" articles

References

REFERENCES

1. Alexiadou, K. , & Doupis, J. (2012). Management of diabetic foot ulcers. Diabetes Therapy, 3(1), 4. https://doi.org/10.1007/s13300-012-0004-9
1. An, Y. , Liu, W. J. , Xue, P. , Ma, Y. , Zhang, L. Q. , Zhu, B. , Qi, M. , Li, L. Y. , Zhang, Y. J. , Wang, Q. T. , & Jin, Y. (2018). Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion. Cell Death & Disease, 9(2), 58. https://doi.org/10.1038/s41419-017-0082-8.
1. Bagonza, J. , Rutebemberwa, E. , & Bazeyo, W. (2015). Adherence to anti diabetic medication among patients with diabetes in eastern Uganda; a cross sectional study. BMC Health Services Research, 15, 168. https://doi.org/10.1186/s12913-015-0820-5
1. Bekele, F. , & Chelkeba, L. (2020). Amputation rate of diabetic foot ulcer and associated factors in diabetes mellitus patients admitted to Nekemte referral hospital, western Ethiopia: Prospective observational study. Journal of Foot and Ankle Research, 13(1), 65. https://doi.org/10.1186/s13047-020-00433-9
1. Chen, C. Y. , Rao, S. S. , Ren, L. , Hu, X. K. , Tan, Y. J. , Hu, Y. , Luo, J. , Liu, Y. W. , Yin, H. , Huang, J. , Cao, J. , Wang, Z. X. , Liu, Z. Z. , Liu, H. M. , Tang, S. Y. , Xu, R. , & Xie, H. (2018). Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics, 8(6), 1607-1623. https://doi.org/10.7150/thno.22958

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Wiley
Other Literature Sources
- scite Smart Citations
Miscellaneous
- NCI CPTAC Assay Portal

[1] Alexiadou, K. , & Doupis, J. (2012). Management of diabetic foot ulcers. Diabetes Therapy, 3(1), 4. https://doi.org/10.1007/s13300-012-0004-9

[2] Alexiadou, K. , & Doupis, J. (2012). Management of diabetic foot ulcers. Diabetes Therapy, 3(1), 4. https://doi.org/10.1007/s13300-012-0004-9

[3] An, Y. , Liu, W. J. , Xue, P. , Ma, Y. , Zhang, L. Q. , Zhu, B. , Qi, M. , Li, L. Y. , Zhang, Y. J. , Wang, Q. T. , & Jin, Y. (2018). Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion. Cell Death & Disease, 9(2), 58. https://doi.org/10.1038/s41419-017-0082-8.

[4] An, Y. , Liu, W. J. , Xue, P. , Ma, Y. , Zhang, L. Q. , Zhu, B. , Qi, M. , Li, L. Y. , Zhang, Y. J. , Wang, Q. T. , & Jin, Y. (2018). Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion. Cell Death & Disease, 9(2), 58. https://doi.org/10.1038/s41419-017-0082-8.

[5] Bagonza, J. , Rutebemberwa, E. , & Bazeyo, W. (2015). Adherence to anti diabetic medication among patients with diabetes in eastern Uganda; a cross sectional study. BMC Health Services Research, 15, 168. https://doi.org/10.1186/s12913-015-0820-5

[6] Bagonza, J. , Rutebemberwa, E. , & Bazeyo, W. (2015). Adherence to anti diabetic medication among patients with diabetes in eastern Uganda; a cross sectional study. BMC Health Services Research, 15, 168. https://doi.org/10.1186/s12913-015-0820-5

[7] Bekele, F. , & Chelkeba, L. (2020). Amputation rate of diabetic foot ulcer and associated factors in diabetes mellitus patients admitted to Nekemte referral hospital, western Ethiopia: Prospective observational study. Journal of Foot and Ankle Research, 13(1), 65. https://doi.org/10.1186/s13047-020-00433-9

[8] Bekele, F. , & Chelkeba, L. (2020). Amputation rate of diabetic foot ulcer and associated factors in diabetes mellitus patients admitted to Nekemte referral hospital, western Ethiopia: Prospective observational study. Journal of Foot and Ankle Research, 13(1), 65. https://doi.org/10.1186/s13047-020-00433-9

[9] Chen, C. Y. , Rao, S. S. , Ren, L. , Hu, X. K. , Tan, Y. J. , Hu, Y. , Luo, J. , Liu, Y. W. , Yin, H. , Huang, J. , Cao, J. , Wang, Z. X. , Liu, Z. Z. , Liu, H. M. , Tang, S. Y. , Xu, R. , & Xie, H. (2018). Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics, 8(6), 1607-1623. https://doi.org/10.7150/thno.22958

[10] Chen, C. Y. , Rao, S. S. , Ren, L. , Hu, X. K. , Tan, Y. J. , Hu, Y. , Luo, J. , Liu, Y. W. , Yin, H. , Huang, J. , Cao, J. , Wang, Z. X. , Liu, Z. Z. , Liu, H. M. , Tang, S. Y. , Xu, R. , & Xie, H. (2018). Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics, 8(6), 1607-1623. https://doi.org/10.7150/thno.22958

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Serum exosomes accelerate diabetic wound healing by promoting angiogenesis and ECM formation

Affiliations

Serum exosomes accelerate diabetic wound healing by promoting angiogenesis and ECM formation

Authors

Affiliations

Abstract

Similar articles

Cited by

References

REFERENCES

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Miscellaneous