间充质干细胞来源的外泌体在皮肤病中的作用

doi:10.35541/cjd.20220881

中华皮肤科杂志 ›› 2025, e20220881.doi: 10.35541/cjd.20220881

间充质干细胞来源的外泌体在皮肤病中的作用

许焯红¹ 胡煜² 顾恒²

¹北京协和医学院中国医学科学院皮肤病医院皮肤病研究所，南京 210042；²中国医学科学院北京协和医学院皮肤病医院，南京 210042

收稿日期:2022-12-08 修回日期:2024-07-01 发布日期:2025-01-23
通讯作者: 顾恒 E-mail:guheng@aliyun.com
基金资助:
国家自然科学基金（82273552、82203947、82073445）；江苏省自然科学基金（BK20210049）；中国医学科学院医学与健康科技创新工程项目（CIFMS-2021-I2M-1-001）

Role of mesenchymal stem cell-derived exosomes in skin diseases

Xu Zhuohong¹, Hu Yu², Gu Heng²

¹Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China; ²Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China

Received:2022-12-08 Revised:2024-07-01 Published:2025-01-23
Contact: Gu Heng E-mail:guheng@aliyun.com
Supported by:
National Natural Science Foundation of China （82273552, 82203947, 82073445）; Jiangsu Province Natural Science Foundation （BK20210049）; CAMS Innovation Fund for Medical Sciences（CIFMS-2021-I2M-1-001）

摘要/Abstract

摘要： 【摘要】间充质干细胞是具有分化为不同类型细胞潜力的多能干细胞。许多证据表明，间充质干细胞主要通过旁分泌效应发挥生物学功能，其旁分泌效应可由外泌体介导。外泌体可以携带DNA、RNA、脂质、蛋白质，并将它们引入受体细胞，产生各种生物学效应。近年来，已有多项研究证实了多种来源间充质干细胞外泌体具有治疗皮肤病的作用。本文就来源于间充质干细胞的外泌体生物学特性和功能及其在皮肤病治疗中的研究作用进行综述。

关键词: 外泌体, 间质干细胞, 治疗, 红斑狼疮, 系统性, 皮炎, 特应性, 银屑病

Abstract: 【Abstract】 Mesenchymal stem cells are pluripotent stem cells with the potential to differentiate into various types of cells. Many studies have shown that mesenchymal stem cells primarily exert their biological functions through paracrine effects, which can be mediated by exosomes. Exosomes can carry DNA, RNA, lipids, and proteins, and introduce them into recipient cells to produce various biological effects. In recent years, a lot of studies have confirmed the therapeutic effects of mesenchymal stem cell?derived exosomes from various sources on skin diseases. This review summarizes the biological characteristics and functions of mesenchymal stem cell-derived exosomes and their roles in the treatment of skin diseases.

Key words: Exosomes, Mesenchymal stem cells, Therapy, Lupus erythematosus, systemic, Dermatitis, atopic, Psoriasis

许焯红胡煜顾恒. 间充质干细胞来源的外泌体在皮肤病中的作用[J]. 中华皮肤科杂志, 2025,e20220881. doi:10.35541/cjd.20220881

Xu Zhuohong, Hu Yu, Gu Heng. Role of mesenchymal stem cell-derived exosomes in skin diseases[J]. Chinese Journal of Dermatology,2025,e20220881. doi:10.35541/cjd.20220881

参考文献 39

［1］	Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells［J］. Science, 1999,284（5411）:143⁃147. doi: 10.1126/science.284.5411.143.
［2］	Xunian Z, Kalluri R. Biology and therapeutic potential of mesenchymal stem cell⁃derived exosomes［J］. Cancer Sci, 2020,111（9）:3100⁃3110. doi: 10.1111/cas.14563.
［3］	Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes［J］. Science, 2020,367（6478）:eaau6977. doi: 10.1126/science.aau6977.
［4］	Kusuma GD, Barabadi M, Tan JL, et al. To Protect and to preserve: novel preservation strategies for extracellular vesicles［J］. Front Pharmacol, 2018,9:1199. doi: 10.3389/fphar.2018. 01199.
［5］	Chen J, Chen J, Cheng Y, et al. Mesenchymal stem cell⁃derived exosomes protect beta cells against hypoxia⁃induced apoptosis via miR⁃21 by alleviating ER stress and inhibiting p38 MAPK phosphorylation［J］. Stem Cell Res Ther, 2020,11（1）:97. doi: 10.1186/s13287⁃020⁃01610⁃0.
［6］	Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome: a novel stem cell⁃based therapy for cardiovascular disease［J］. Regen Med, 2011,6（4）:481⁃492. doi: 10.2217/rme.11.35.
［7］	Sipos F, Mzes G. Controversies in therapeutic application of mesenchymal stem cell⁃derived secretome［J］. BIOCELL, 2022, 46（4）: 4.doi: 10.32604/biocell.2022.018200.
［8］	Toh WS, Lai RC, Zhang B, et al. MSC exosome works through a protein⁃based mechanism of action［J］. Biochem Soc Trans, 2018,46（4）:843⁃853. doi: 10.1042/BST20180079.
［9］	Tang XD, Shi L, Monsel A, et al. Mesenchymal stem cell microvesicles attenuate acute lung injury in mice partly mediated by Ang⁃1 mRNA［J］. Stem Cells, 2017,35（7）:1849⁃1859. doi: 10.1002/stem.2619.
［10］	Katsuda T, Ochiya T. Molecular signatures of mesenchymal stem cell⁃derived extracellular vesicle⁃mediated tissue repair［J］. Stem Cell Res Ther, 2015,6:212. doi: 10.1186/s13287⁃015⁃0214⁃y.
［11］	Ge L, Xun C, Li W, et al. Extracellular vesicles derived from hypoxia⁃preconditioned olfactory mucosa mesenchymal stem cells enhance angiogenesis via miR⁃612［J］. J Nanobiotechnology, 2021,19（1）:380. doi: 10.1186/s12951⁃021⁃01126⁃6.
［12］	Tavasolian F, Hosseini AZ, Soudi S, et al. miRNA⁃146a improves immunomodulatory effects of MSC⁃derived exosomes in rheumatoid arthritis［J］. Curr Gene Ther, 2020,20（4）:297⁃312. doi: 10.2174/1566523220666200916120708.
［13］	Zhang Y, Pan Y, Liu Y, et al. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor⁃β receptor inhibition［J］. Stem Cell Res Ther, 2021,12（1）:434. doi: 10.1186/s13287⁃021⁃02517⁃0.
［14］	Gezer U, Özgür E, Cetinkaya M, et al. Long non⁃coding RNAs with low expression levels in cells are enriched in secreted exosomes［J］. Cell Biol Int, 2014,38（9）:1076⁃1079. doi: 10. 1002/cbin.10301.
［15］	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⁃826. doi: 10.1016/j.omtn.2019.11.034.
［16］	Dou R, Zhang X, Xu X, et al. Mesenchymal stem cell exosomal tsRNA⁃21109 alleviate systemic lupus erythematosus by inhibiting macrophage M1 polarization［J］. Mol Immunol, 2021,139:106⁃114. doi: 10.1016/j.molimm.2021.08.015.
［17］	Lai RC, Tan SS, Teh BJ, et al. Proteolytic potential of the MSC exosome proteome: implications for an exosome⁃mediated delivery of therapeutic proteasome［J］. Int J Proteomics, 2012,2012:971907. doi: 10.1155/2012/971907.
［18］	Zhang B, Wang M, Gong A, et al. HucMSC⁃exosome mediated⁃Wnt4 signaling is required for cutaneous wound healing［J］. Stem Cells, 2015,33（7）:2158⁃2168. doi: 10.1002/stem.1771.
［19］	Zhang B, Shi Y, Gong A, 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⁃2500. doi: 10.1002/stem.2432.
［20］	Shabbir A, Cox A, Rodriguez⁃Menocal L, et al. Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro［J］. Stem Cells Dev, 2015,24（14）:1635⁃1647. doi: 10.1089/scd. 2014.0316.
［21］	Liu H, Liang Z, Wang F, et al. Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage⁃ dependent mechanism［J］. JCI Insight, 2019,4（24）:e131273. doi: 10.1172/jci.insight.131273.
［22］	Yang S, Liang X, Song J, et al. A novel therapeutic approach for inflammatory bowel disease by exosomes derived from human umbilical cord mesenchymal stem cells to repair intestinal barrier via TSG⁃6［J］. Stem Cell Res Ther, 2021,12（1）:315. doi: 10.1186/s13287⁃021⁃02404⁃8.
［23］	Ha DH, Kim HK, Lee J, et al. Mesenchymal stem/stromal cell⁃derived exosomes for immunomodulatory therapeutics and skin regeneration［J］. Cells, 2020,9（5）:1157. doi: 10.3390/cells9051157.
［24］	Silachev DN, Goryunov KV, Shpilyuk MA, et al. Effect of MSCs and MSC⁃derived extracellular vesicles on human blood coagulation［J］. Cells, 2019,8（3）:258. doi: 10.3390/cells803 0258.
［25］	夏娜, 高超, 刘璇, 等. 脐带间充质干细胞外泌体对急性皮肤创面愈合的初步研究［J］.中华皮肤科杂志, 2022,55（5）:382⁃388. doi: 10.35541/cjd.20210831.
［26］	Zhao W, Zhang R, Zang C, et al. Exosome derived from mesenchymal stem cells alleviates pathological scars by inhibiting the proliferation, migration and protein expression of fibroblasts via delivering miR⁃138⁃5p to target SIRT1［J］. Int J Nanomedicine, 2022,17:4023⁃4038. doi: 10.2147/IJN.S377317.
［27］	Yang C, Sun J, Tian Y, et al. Immunomodulatory effect of MSCs and MSCs⁃derived extracellular vesicles in systemic lupus erythematosus［J］. Front Immunol, 2021,12:714832. doi: 10. 3389/fimmu.2021.714832.
［28］	Bolandi Z, Mokhberian N, Eftekhary M, et al. Adipose derived mesenchymal stem cell exosomes loaded with miR⁃10a promote the differentiation of Th17 and Treg from naive CD4（+） T cell［J］. Life Sci, 2020,259:118218. doi: 10.1016/j.lfs.2020.118218.
［29］	Adamo A, Brandi J, Caligola S, et al. Extracellular vesicles mediate mesenchymal stromal cell⁃dependent regulation of B cell PI3K⁃AKT signaling pathway and actin cytoskeleton［J］. Front Immunol, 2019,10:446. doi: 10.3389/fimmu.2019.00446.
［30］	Shahir M, Mahmoud Hashemi S, Asadirad A, et al. Effect of mesenchymal stem cell⁃derived exosomes on the induction of mouse tolerogenic dendritic cells［J］. J Cell Physiol, 2020,235（10）:7043⁃7055. doi: 10.1002/jcp.29601.
［31］	Dong B, Wang C, Zhang J, et al. Exosomes from human umbilical cord mesenchymal stem cells attenuate the inflammation of severe steroid⁃resistant asthma by reshaping macrophage polarization［J］. Stem Cell Res Ther, 2021,12（1）:204. doi: 10. 1186/s13287⁃021⁃02244⁃6.
［32］	Ye Z, Liang Y, Lin B, et al. Gingiva⁃derived mesenchymal stem cells attenuate imiquimod⁃ （IMQ⁃） induced murine psoriasis⁃like skin inflammation［J］. Stem Cells Int, 2022,2022:6544514. doi: 10.1155/2022/6544514.
［33］	韩齐心, 牛旭平, 刘佳, 等. 间充质干细胞及其外泌体与Th17/Treg对银屑病发病机制的研究进展［J］.中华皮肤科杂志, 2020,53（2）:151⁃154. doi: 10.35541/cjd.20190012.
［34］	Ghoreschi K, Balato A, Enerbäck C, et al. Therapeutics targeting the IL⁃23 and IL⁃17 pathway in psoriasis［J］. Lancet, 2021,397（10275）:754⁃766. doi: 10.1016/S0140⁃6736（21）00184⁃7.
［35］	Xu F, Fei Z, Dai H, et al. Mesenchymal stem cell⁃derived extracellular vesicles with high PD⁃L1 Expression for Autoimmune Diseases Treatment［J］. Adv Mater, 2022,34（1）:e2106265. doi: 10.1002/adma.202106265.
［36］	Shin KO, Ha DH, Kim JO, et al. Exosomes from human adipose tissue⁃derived mesenchymal stem cells promote epidermal barrier repair by inducing de novo synthesis of ceramides in atopic dermatitis［J］. Cells, 2020,9（3）:680. doi: 10.3390/cells 9030680.
［37］	Deng M, Yu TZ, Li D, et al. Human umbilical cord mesenchymal stem cell⁃derived and dermal fibroblast⁃derived extracellular vesicles protect dermal fibroblasts from ultraviolet radiation⁃induced photoaging in vitro［J］. Photochem Photobiol Sci, 2020,19（3）:406⁃414. doi: 10.1039/c9pp00421a.
［38］	Zhang K, Yu L, Li FR, et al. Topical application of exosomes derived from human umbilical cord mesenchymal stem cells in combination with sponge spicules for treatment of photoaging［J］. Int J Nanomedicine, 2020,15:2859⁃2872. doi: 10.2147/IJN.S249751.
［39］	Ding Q, Sun R, Wang P, et al. Protective effects of human induced pluripotent stem cell⁃derived exosomes on high glucose⁃induced injury in human endothelial cells［J］. Exp Ther Med, 2018,15（6）:4791⁃4797. doi: 10.3892/etm.2018.6059.

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间充质干细胞来源的外泌体在皮肤病中的作用

Role of mesenchymal stem cell-derived exosomes in skin diseases

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