Extracellular Vesicles Derived from Mesenchymal Stem Cells Promote Wound Healing and Skin Regeneration by Modulating Multiple Cellular Changes: A Brief Review

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2023 Aug 26

PMID 37628568

Authors

Weiyuan Zhang

Yang Ling

Yang Sun

Fengjun Xiao

Lisheng Wang

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are biologically active substances secreted by MSCs into the extracellular matrix that play an immunomodulatory role in skin damage repair. To investigate the mechanism of MSC-EVs in reducing inflammation, promoting angiogenesis, promoting the proliferation and migration of epithelial cells and fibroblasts, and extracellular matrix remodeling during wound healing, we focused on the effects of EVs on multiple cell types at various stages of skin injury. A literature review was conducted to explore related research on the influence of MSC-EVs on the types of cells involved in wound healing. MSC-EVs show a strong regulatory ability on immune cells involved in the regulation of inflammation, including macrophages, neutrophils, and T cells, and other cells involved in tissue proliferation and remodeling, such as fibroblasts, keratinocytes, and endothelial cells, during wound healing in in vitro and in vivo experiments, which substantially promoted the understanding of wound healing in the field of trauma medicine. MSC-EVs have potential applications in combating poor skin wound healing. Elucidating the mechanism of action of EVs in the wound-healing process would greatly advance the understanding of therapeutic wound healing.

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References

Ramos T, Sanchez-Abarca L, Muntion S, Preciado S, Puig N, Lopez-Ruano G . MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry. Cell Commun Signal. 2016; 14:2. PMC: 4709865. DOI: 10.1186/s12964-015-0124-8. View

Koliaraki V, Prados A, Armaka M, Kollias G . The mesenchymal context in inflammation, immunity and cancer. Nat Immunol. 2020; 21(9):974-982. DOI: 10.1038/s41590-020-0741-2. View

Son D, Harijan A . Overview of surgical scar prevention and management. J Korean Med Sci. 2014; 29(6):751-7. PMC: 4055805. DOI: 10.3346/jkms.2014.29.6.751. View

Hade M, Suire C, Mossell J, Suo Z . Extracellular vesicles: Emerging frontiers in wound healing. Med Res Rev. 2022; 42(6):2102-2125. DOI: 10.1002/med.21918. View

Zhao X, Fu L, Zou H, He Y, Pan Y, Ye L . Optogenetic engineered umbilical cord MSC-derived exosomes for remodeling of the immune microenvironment in diabetic wounds and the promotion of tissue repair. J Nanobiotechnology. 2023; 21(1):176. PMC: 10236791. DOI: 10.1186/s12951-023-01886-3. View

Zhao B, Zhang Y, Han S, Zhang W, Zhou Q, Guan H . Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar formation. J Mol Histol. 2017; 48(2):121-132. DOI: 10.1007/s10735-017-9711-x. View

Cao W, Cao K, Cao J, Wang Y, Shi Y . Mesenchymal stem cells and adaptive immune responses. Immunol Lett. 2015; 168(2):147-53. DOI: 10.1016/j.imlet.2015.06.003. View

Wang J, Xia J, Huang R, Hu Y, Fan J, Shu Q . Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization. Stem Cell Res Ther. 2020; 11(1):424. PMC: 7522905. DOI: 10.1186/s13287-020-01937-8. View

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

10.

Liu D, Kou X, Chen C, Liu S, Liu Y, Yu W . Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors. Cell Res. 2018; 28(9):918-933. PMC: 6123409. DOI: 10.1038/s41422-018-0070-2. View

11.

Kourembanas S . Exosomes: vehicles of intercellular signaling, biomarkers, and vectors of cell therapy. Annu Rev Physiol. 2014; 77:13-27. DOI: 10.1146/annurev-physiol-021014-071641. View

12.

Xu S, Liu C, Ji H . Concise Review: Therapeutic Potential of the Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Radiation-Induced Lung Injury: Progress and Hypotheses. Stem Cells Transl Med. 2019; 8(4):344-354. PMC: 6431606. DOI: 10.1002/sctm.18-0038. View

13.

Levy D, Nourmohammadi Abadchi S, Shababi N, Ravari M, Pirolli N, Bergeron C . Induced Pluripotent Stem Cell-Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti-Inflammatory Immunomodulatory Mechanism. Adv Healthc Mater. 2023; 12(26):e2300879. PMC: 10592465. DOI: 10.1002/adhm.202300879. View

14.

Zhou X, Brown B, Siegel A, El Masry M, Zeng X, Song W . Exosome-Mediated Crosstalk between Keratinocytes and Macrophages in Cutaneous Wound Healing. ACS Nano. 2020; 14(10):12732-12748. PMC: 7970718. DOI: 10.1021/acsnano.0c03064. View

15.

FRIEDENSTEIN A, Gorskaja J, Kulagina N . Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 1976; 4(5):267-74. View

16.

Yang C, Chen Y, Li F, You M, Zhong L, Li W . The biological changes of umbilical cord mesenchymal stem cells in inflammatory environment induced by different cytokines. Mol Cell Biochem. 2018; 446(1-2):171-184. DOI: 10.1007/s11010-018-3284-1. View

17.

Todorova D, Simoncini S, Lacroix R, Sabatier F, Dignat-George F . Extracellular Vesicles in Angiogenesis. Circ Res. 2017; 120(10):1658-1673. PMC: 5426696. DOI: 10.1161/CIRCRESAHA.117.309681. View

18.

Shen C, Tao C, Zhang A, Li X, Guo Y, Wei H . Exosomal microRNA⁃93⁃3p secreted by bone marrow mesenchymal stem cells downregulates apoptotic peptidase activating factor 1 to promote wound healing. Bioengineered. 2021; 13(1):27-37. PMC: 8805970. DOI: 10.1080/21655979.2021.1997077. View

19.

Ti D, Hao H, Tong C, Liu J, Dong L, Zheng J . LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. J Transl Med. 2015; 13:308. PMC: 4575470. DOI: 10.1186/s12967-015-0642-6. View

20.

Jiang M, Fang H, Shao S, Dang E, Zhang J, Qiao P . Keratinocyte exosomes activate neutrophils and enhance skin inflammation in psoriasis. FASEB J. 2019; 33(12):13241-13253. DOI: 10.1096/fj.201900642R. View