Research progress of the effect and mechanism of exosomes derived from mesenchymal stem cells in promoting skin wound healing

间充质干细胞分泌的外泌体是干细胞发挥生物学效应的重要载体。通过与靶细胞融合，外泌体可以转运干细胞中的活性蛋白和多种类型的核酸进入皮肤损伤部位的靶细胞。现已证实，间充质干细胞外泌体可通过调控炎症反应、促进细胞增殖迁移、促进血管生成和调控基质重建促进创面愈合并抑制瘢痕形成，是促进创面愈合生物治疗的新思路。近年来的研究发现，对间充质干细胞外泌体进行预处理或调整外泌体的给药方式，能获得更加显著的创面治疗效果。针对间充质干细胞外泌体在创面愈合中发挥的积极作用，本文对间充质干细胞来源的外泌体在创面修复中发挥作用的机制、外泌体预处理调控方法及给药方式作一综述，旨在为外泌体在伤口愈合中的作用提供全面理解。

Exosomes derived from mesenchymal stem cells are important carriers for mesenchymal stem cells to play biological effects. Exosomes can transport active proteins and various types of nucleic acids in stem cells into target cells by cell fusion. It has been confirmed that exosomes derived from mesenchymal stem cells can promote scarless wound healing by regulating inflammation， promoting cell proliferation and migrate， inhibiting cell apoptosis， promoting angiogenesis and regulating matrix remodelling. It has been proved that the exosome is a new biotherapy method to promote wound healing. In recent years， new studies have found that pretreatment of exosomes or adjusting the administration mode of exosomes can achieve more significant wound healing effects. In view of the positive role of mesenchymal stem cell exosomes in wound healing， this paper reviews the mechanism of the role of exosomes derived from mesenchymal stem cells in wound healing and the methods of engineering exosomes and administration methods in order to provide a comprehensive understanding of the role of exosomes in wound healing.

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Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences ›› 2022, Vol. 43 ›› Issue (8) : 620-625. DOI: 10.3969/j.issn.2097-0005.2022.08.014

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Research progress of the effect and mechanism of exosomes derived from mesenchymal stem cells in promoting skin wound healing

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Received	Published
2022-02-18	2022-08-25
Issue Date
2022-09-02

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mesenchymal stem cell/exosome/wound healing/engineering/administration

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Haiyan CONG, Na WANG, Xin CHANG, Haitao WANG, Jincun YANG.Research progress of the effect and mechanism of exosomes derived from mesenchymal stem cells in promoting skin wound healing[J]. Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences. 2022, 43(8): 620-625 https://doi.org/10.3969/j.issn.2097-0005.2022.08.014

References

1	Martino MM， Briquez PS， Gü? E， et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing［J］. Science， 2014， 343（6173）： 885.
2	Andreadis ST， Geer DJ. Biomimetic approaches to protein and gene delivery for tissue regeneration［J］. Trends Biotechnol， 2006， 24（7）： 331.
3	Saki N， Jalalifar MA， Soleimani M， et al. Adverse effect of high glucose concentration on stem cell therapy［J］. Int J Hematol Oncol Stem Cell Res， 2013， 7（3）： 34.
4	Chramiec A， Vunjak-Novakovic G. Tissue engineered models of healthy and malignant human bone marrow［J］. Adv Drug Deliv Rev， 2019， 140： 78.
5	DiLoreto R， Khush K， De Vlaminck I. Precision monitoring of immunotherapies in solid organ and hematopoietic stem cell transplantation［J］. Adv Drug Deliv Rev， 2017， 114： 272.
6	Jing H， He XM， Zheng JH. Exosomes and regenerative medicine： state of the art and perspectives［J］. Transl Res， 2018， 196： 1.
7	Chen KH， Chen CH， Wallace CG， et al. Intravenous administration of xenogenic adipose-derived mesenchymal stem cells （ADMSC） and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke［J］. Oncotarget， 2016， 7（46）： 74537.
8	Mathivanan S， Ji H， Simpson RJ. Exosomes： extracellular organelles important in intercellular communication［J］. J Proteomics， 2010， 73（10）： 1907.
9	Borges FT， Melo SA， ?zdemir BC， et al. TGF-β1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis［J］. J Am Soc Nephrol， 2013， 24（3）： 385.
10	Wolfers J， Lozier A， Raposo G， et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming［J］. Nat Med， 2001， 7（3）： 297.
11	Skokos D， Botros HG， Demeure C， et al. Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responsesin vivo［J］. J Immunol， 2003， 170（6）： 3037.
12	Caby MP， Lankar D， Vincendeau-Scherrer C， et al. Exosomal-like vesicles are present in human blood plasma［J］. Int Immunol， 2005， 17（7）： 879.
13	Pisitkun T， Shen RF， Knepper MA. Identification and proteomic profiling of exosomes in human urine［J］. Proc Natl Acad Sci U S A， 2004， 101（36）： 13368.
14	Palanisamy V， Sharma S， Deshpande A， et al. Nanostructural and transcriptomic analyses of human saliva derived exosomes［J］. PLoS One， 2010， 5（1）： e8577.
15	高斌，熊莹晖，黄泽炳，等. 乙肝相关性肝细胞癌患者血清外泌体miR-1290水平的变化及其诊断价值［J］. 中国普通外科杂志， 2019， 28（1）： 31.
16	Li A， Yu J， Kim H， et al. MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls［J］. Clin Cancer Res， 2013， 19（13）： 3600.
17	Zhao B， Zhang YJ， Han SC， et al. Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar formation［J］. J Mol Histol， 2017， 48（2）： 121.
18	张静，易阳艳，阳水发，等. 脂肪干细胞来源外泌体对人脐静脉血管内皮细胞增殖、迁移及管样分化的影响［J］. 中国修复重建外科杂志， 2018， 32（10）： 1351.
19	Liu JW， Yan ZX， Yang FJ， et al. Exosomes derived from human umbilical cord mesenchymal stem cells accelerate cutaneous wound healing by enhancing angiogenesis through delivering angiopoietin-2［J］. Stem Cell Rev Rep， 2021， 17（2）： 305.
20	Liu W， Yu MY， Xie D， et al. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway［J］. Stem Cell Res Ther， 2020， 11（1）： 259.
21	Ti DD， Hao HJ， Tong C， et al. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b［J］. J Transl Med， 2015， 13： 308.
22	Ti DD， Hao HJ， Fu XB， et al. Mesenchymal stem cells-derived exosomal microRNAs contribute to wound inflammation［J］. Sci China Life Sci， 2016， 59（12）： 1305.
23	Li X， Liu LY， Yang J， et al. Exosome derived from human umbilical cord mesenchymal stem cell mediates MiR-181c attenuating burn-induced excessive inflammation［J］. EBioMedicine， 2016， 8： 72.
24	Zhang JY， Guan JJ， Niu X， et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis［J］. J Transl Med， 2015， 13： 49.
25	Hu L， Wang J， Zhou X， et al. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts［J］. Sci Rep， 2016， 6： 32993.
26	Zhang W， Bai XZ， Zhao B， et al. Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway［J］. Exp Cell Res， 2018， 370（2）： 333.
27	Zhang B， Wang M， Gong AH， et al. HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing［J］. Stem Cells， 2015， 33（7）： 2158.
28	Grainger S， Willert K. Mechanisms of Wnt signaling and control［J］. Wiley Interdiscip Rev Syst Biol Med， 2018， 10（5）： e1422.
29	Wang X， Jiao Y， Pan Y， et al. Fetal dermal mesenchymal stem cell-derived exosomes accelerate cutaneous wound healing by activating notch signaling［J］. Stem Cells Int， 2019， 2019： 2402916.
30	Yang C， Luo L， Bai XZ， et al. 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［J］. Arch Biochem Biophys， 2020， 681： 108259.
31	He L， Zhu C， Jia J， et al. ADSC-exos containing MALAT1 promotes wound healing by targeting miR-124 through activating Wnt/β-catenin pathway［J］. Biosci Rep， 2020， 40（5）： BSR20192549.
32	Li B， Luan S， Chen J， et al. The MSC-derived exosomal lncRNA H19 promotes wound healing in diabetic foot ulcers by upregulating PTEN via microRNA-152-3p［J］. Mol Ther Nucleic Acids， 2020， 19： 814.
33	Kong PR， Xie XY， Li F， et al. Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki （GK） rats［J］. Biochem Biophys Res Commun， 2013， 438（2）： 410.
34	Liu JW， Yan ZX， Yang FJ， et al. Exosomes derived from human umbilical cord mesenchymal stem cells accelerate cutaneous wound healing by enhancing angiogenesis through delivering angiopoietin-2［J］. Stem Cell Rev Rep， 2021， 17（2）： 305.
35	Anderson JD， Johansson HJ， Graham CS， et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling［J］. Stem Cells， 2016， 34（3）： 601.
36	Liang XL， Zhang LN， Wang SH， et al. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a［J］. J Cell Sci， 2016， 129（11）： 2182.
37	Hu Y， Rao SS， Wang ZX， et al. Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function［J］. Theranostics， 2018， 8（1）： 169.
38	Fang S， Xu C， Zhang YT， et al. Umbilical cord-derived mesenchymal stem cell-derived exosomal microRNAs suppress myofibroblast differentiation by inhibiting the transforming growth factor-β/SMAD2 pathway during wound healing［J］. Stem Cells Transl Med， 2016， 5（10）： 1425.
39	Zhang B， Shi YH， Gong AH， et al. HucMSC exosome-delivered 14-3-3ζ orchestrates self-control of the Wnt response via modulation of YAP during cutaneous regeneration［J］. Stem Cells， 2016， 34（10）： 2485.
40	Wang L， Hu L， Zhou X， et al. Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodelling［J］. Sci Rep， 2017， 7（1）： 13321.
41	Lv QJ， Deng JF， Chen Y， et al. Engineered human adipose stem-cell-derived exosomes loaded with miR-21-5p to promote diabetic cutaneous wound healing［J］. Mol Pharm， 2020， 17（5）： 1723.
42	Zhang L， Ouyang PR， He GL， et al. Exosomes from microRNA-126 overexpressing mesenchymal stem cells promote angiogenesis by targeting the PIK3R2-mediated PI3K/Akt signalling pathway［J］. J Cell Mol Med， 2021， 25（4）： 2148.
43	Li X， Xie XY， Lian WS， et al. Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model［J］. Exp Mol Med， 2018， 50（4）： 1.
44	Qiu XY， Liu J， Zheng CX， et al. Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis［J］. Cell Prolif， 2020， 53（8）： e12830.
45	Yu MY， Liu W， Li JX， et al. Exosomes derived from atorvastatin-pretreated MSC accelerate diabetic wound repair by enhancing angiogenesis via AKT/eNOS pathway［J］. Stem Cell Res Ther， 2020， 11（1）： 350.
46	Wu D， Kang L， Tian JJ， et al. Exosomes derived from bone mesenchymal stem cells with the stimulation of Fe₃O₄nanoparticles and static magnetic field enhance wound healing through upregulated miR-21-5p［J］. Int J Nanomedicine， 2020， 15： 7979.
47	Liu XL， Yang YL， Li Y， et al. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration［J］. Nanoscale， 2017， 9（13）： 4430.
48	Wang CG， Wang M， Xu TZ， et al. Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration［J］. Theranostics， 2019， 9（1）： 65.
49	Shi Q， Qian ZY， Liu DH， et al. GMSC-Derived exosomes combined with a chitosan/silk hydrogel sponge accelerates wound healing in a diabetic rat skin defect model［J］. Front Physiol， 2017， 8： 904.
50	Yang JY， Chen ZY， Pan DY， et al. Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration［J］. Int J Nanomedicine， 2020， 15： 5911.
51	Shafei S， Khanmohammadi M， Heidari R， et al. Exosome loaded alginate hydrogel promotes tissue regeneration in full-thickness skin wounds： anin vivostudy［J］. J Biomed Mater Res A， 2020， 108（3）： 545.
52	Nooshabadi VT， Khanmohamadi M， Valipour E， et al. Impact of exosome-loaded chitosan hydrogel in wound repair and layered dermal reconstitution in mice animal model［J］. J Biomed Mater Res A， 2020， 108（11）： 2138.
53	Xu N， Wang LL， Guan JJ， et al. Wound healing effects of aCurcuma zedoariapolysaccharide with platelet-rich plasma exosomes assembled on chitosan/silk hydrogel sponge in a diabetic rat model［J］. Int J Biol Macromol， 2018， 117： 102.
54	Wang CY， Liang CY， Wang R， et al. The fabrication of a highly efficient self-healing hydrogel from natural biopolymers loaded with exosomes for the synergistic promotion of severe wound healing［J］. Biomater Sci， 2019， 8（1）： 313.