Extracellular Vesicles in Skin Wound Healing

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2021 Aug 28

PMID 34451909

Citations 47

Authors

Deimante Narauskaite

Gabriele Vydmantaite

Justina Rusteikaite

Revathi Sampath

Akvile Rudaityte

Gabija Stasyte

Maria Isabel Aparicio Calvente

Aiste Jekabsone

Affiliations

Soon will be listed here.

Abstract

Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signaling takes part in all four wound healing phases: hemostasis, inflammation, proliferation, and remodeling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration, and treatment of dermal diseases, including the stem cell-derived, plant-derived, and engineered EVs.

Citing Articles

The Role of Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in Modulating Dermal Fibroblast Activity: A Pathway to Enhanced Tissue Regeneration.

Barathan M, Ham K, Wong H, Law J Biology (Basel). 2025; 14(2).

PMID: 40001918 PMC: 11852171. DOI: 10.3390/biology14020150.

Umbilical Cord Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Modulate Skin Matrix Synthesis and Pigmentation.

Kee L, Foo J, How C, Nur Azurah A, Chan H, Mohd Yunus M Int J Nanomedicine. 2025; 20:1561-1578.

PMID: 39931529 PMC: 11807784. DOI: 10.2147/IJN.S497940.

Macrophages: a double-edged sword in female reproduction and disorders.

Park M, Kim Y, Song H Exp Mol Med. 2025; 57(2):285-297.

PMID: 39894821 PMC: 11873061. DOI: 10.1038/s12276-025-01392-6.

Application of novel strategies in chronic wound management with focusing on pressure ulcers: new perspective.

Razavi Z, Aliniay Sharafshadehi S, Yousefi M, Javaheri F, Rahimi Barghani M, Afkhami H Arch Dermatol Res. 2025; 317(1):320.

PMID: 39888392 DOI: 10.1007/s00403-024-03790-8.

Enhancement of skin regeneration through activation of signaling pathway by meyer non-edible callus-derived extracellular vesicles.

Park H, Kang M, Lee G, Kim J J Ginseng Res. 2025; 49(1):34-41.

PMID: 39872281 PMC: 11770231. DOI: 10.1016/j.jgr.2024.08.002.

References

Yang C, Luo L, Bai X, Shen K, Liu K, Wang J . Highly-expressed micoRNA-21 in adipose derived stem cell exosomes can enhance the migration and proliferation of the HaCaT cells by increasing the MMP-9 expression through the PI3K/AKT pathway. Arch Biochem Biophys. 2020; 681:108259. DOI: 10.1016/j.abb.2020.108259. View

Gao S, Chen T, Hao Y, Zhang F, Tang X, Wang D . Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression. Stem Cell Res Ther. 2020; 11(1):56. PMC: 7020560. DOI: 10.1186/s13287-020-1570-9. View

Lv Q, Deng J, Chen Y, Wang Y, Liu B, Liu J . Engineered Human Adipose Stem-Cell-Derived Exosomes Loaded with miR-21-5p to Promote Diabetic Cutaneous Wound Healing. Mol Pharm. 2020; 17(5):1723-1733. DOI: 10.1021/acs.molpharmaceut.0c00177. View

Pan Z, Ye H, Wu D . Recent advances on polymeric hydrogels as wound dressings. APL Bioeng. 2021; 5(1):011504. PMC: 7889296. DOI: 10.1063/5.0038364. View

Heo J, Kim S, Yang C, Choi Y, Song S, Kim H . Human Adipose Mesenchymal Stem Cell-Derived Exosomes: A Key Player in Wound Healing. Tissue Eng Regen Med. 2021; 18(4):537-548. PMC: 8325736. DOI: 10.1007/s13770-020-00316-x. View

Skog J, Wurdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M . Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12):1470-6. PMC: 3423894. DOI: 10.1038/ncb1800. View

Nooshabadi V, Khanmohamadi M, Valipour E, Mahdipour S, Salati A, Malekshahi Z . Impact of exosome-loaded chitosan hydrogel in wound repair and layered dermal reconstitution in mice animal model. J Biomed Mater Res A. 2020; 108(11):2138-2149. DOI: 10.1002/jbm.a.36959. View

Zhang Y, Han F, Gu L, Ji P, Yang X, Liu M . Adipose mesenchymal stem cell exosomes promote wound healing through accelerated keratinocyte migration and proliferation by activating the AKT/HIF-1α axis. J Mol Histol. 2020; 51(4):375-383. DOI: 10.1007/s10735-020-09887-4. View

Kalantari K, Mostafavi E, Afifi A, Izadiyan Z, Jahangirian H, Rafiee-Moghaddam R . Wound dressings functionalized with silver nanoparticles: promises and pitfalls. Nanoscale. 2020; 12(4):2268-2291. DOI: 10.1039/c9nr08234d. View

10.

Limandjaja G, Niessen F, Scheper R, Gibbs S . Hypertrophic scars and keloids: Overview of the evidence and practical guide for differentiating between these abnormal scars. Exp Dermatol. 2020; 30(1):146-161. PMC: 7818137. DOI: 10.1111/exd.14121. View

11.

Das A, Sinha M, Datta S, Abas M, Chaffee S, Sen C . Monocyte and macrophage plasticity in tissue repair and regeneration. Am J Pathol. 2015; 185(10):2596-606. PMC: 4607753. DOI: 10.1016/j.ajpath.2015.06.001. View

12.

Akbari A, Jabbari N, Sharifi R, Ahmadi M, Vahhabi A, Seyedzadeh S . Free and hydrogel encapsulated exosome-based therapies in regenerative medicine. Life Sci. 2020; 249:117447. DOI: 10.1016/j.lfs.2020.117447. View

13.

Qiu X, Liu J, Zheng C, Su Y, Bao L, Zhu B . Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis. Cell Prolif. 2020; 53(8):e12830. PMC: 7445410. DOI: 10.1111/cpr.12830. View

14.

He X, Dong Z, Cao Y, Wang H, Liu S, Liao L . MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing. Stem Cells Int. 2019; 2019:7132708. PMC: 6754952. DOI: 10.1155/2019/7132708. View

15.

Casado-Diaz A, Quesada-Gomez J, Dorado G . Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing. Front Bioeng Biotechnol. 2020; 8:146. PMC: 7062641. DOI: 10.3389/fbioe.2020.00146. View

16.

Meldolesi J . Exosomes and Ectosomes in Intercellular Communication. Curr Biol. 2018; 28(8):R435-R444. DOI: 10.1016/j.cub.2018.01.059. View

17.

Kalan L, Grice E . Fungi in the Wound Microbiome. Adv Wound Care (New Rochelle). 2018; 7(7):247-255. PMC: 6032664. DOI: 10.1089/wound.2017.0756. View

18.

Cooper D, Wang C, Patel R, Trujillo A, Patel N, Prather J . Human Adipose-Derived Stem Cell Conditioned Media and Exosomes Containing Promote Human Dermal Fibroblast Migration and Ischemic Wound Healing. Adv Wound Care (New Rochelle). 2018; 7(9):299-308. PMC: 6158770. DOI: 10.1089/wound.2017.0775. View

19.

Shabbir A, Cox A, Rodriguez-Menocal L, Salgado M, Van Badiavas E . Mesenchymal Stem Cell Exosomes Induce Proliferation and Migration of Normal and Chronic Wound Fibroblasts, and Enhance Angiogenesis In Vitro. Stem Cells Dev. 2015; 24(14):1635-47. PMC: 4499790. DOI: 10.1089/scd.2014.0316. View

20.

Dunnill C, Patton T, Brennan J, Barrett J, Dryden M, Cooke J . Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int Wound J. 2015; 14(1):89-96. PMC: 7950185. DOI: 10.1111/iwj.12557. View