脂肪干细胞外泌体在皮肤瘢痕形成中的作用研究进展

王刘欣; 李云鹏; 吴思默; 张浚睿; 孔亮; 陆斌; 刘富伟; 李治冶

doi:10.3760/cma.j.cn501225-20220308-00057

脂肪干细胞外泌体在皮肤瘢痕形成中的作用研究进展

doi: 10.3760/cma.j.cn501225-20220308-00057

1.
空军军医大学基础医学院，西安　　710032
2.
空军军医大学第三附属医院颌面外科，军事口腔医学国家重点实验室，国家口腔疾病临床医学研究中心，陕西省口腔疾病临床医学研究中心，西安　　710032

基金项目:

国家自然科学基金青年科学基金项目 81801969

国家自然科学基金面上项目 81970988

军事口腔医学国家重点实验室2019年度自主研究课题A类项目 2019ZA08

详细信息

通讯作者:
李治冶，Email：verylzy@163.com

计量
- 文章访问数: 441
- HTML全文浏览量: 118
- PDF下载量: 57
- 被引次数: 0
出版历程
- 收稿日期: 2022-03-08
- 网络出版日期: 2023-03-23

Research progress on the role of adipose-derived stem cell exosomes in skin scar formation

1.
Basic Medical Science Academy of Air Force Medical University, Xi'an 710032, China
2.
Department of Oral and Maxillofacial Surgery, the Third Affiliated Hospital of Air Force Medical University, State Key Laboratory of Military StomatologyNational Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral Diseases, Xi'an 710032, China

Funds:

Youth Science Foundation Project of National Natural Science Foundation of China 81801969

General Program of National Natural Science Foundation of China 81970988

Independent Research Project (Class A) of State Key Laboratory of Military Stomatology in 2019 2019ZA08

More Information

Corresponding author: Li Zhiye, Email: verylzy@163.com

摘要

摘要: 脂肪干细胞外泌体是脂肪干细胞分泌的亚细胞结构，是一种可以运输多种细胞成分并通过旁分泌作用于靶细胞的纳米级膜囊泡，在细胞间的物质交换及信息交流中起着重要作用。瘢痕愈合是皮肤组织损伤后最常见的愈合方式，病理性瘢痕不仅会造成运动功能障碍，还会导致畸形，影响患者外观，给患者带来生活及精神上的压力。近年来，许多研究表明脂肪干细胞外泌体内含有多种生物活性分子，这些分子通过影响成纤维细胞的增殖与迁移及细胞外基质的成分，从而对减少瘢痕形成及无瘢痕创面愈合起重要作用。该文主要对近年来关于脂肪干细胞外泌体在瘢痕形成中的作用及其机制的文献进行综述，并对未来脂肪干细胞外泌体在瘢痕治疗中的应用发展进行展望。
- 外泌体 /
- 瘢痕 /
- 成纤维细胞 /
- 细胞外基质 /
- 脂肪干细胞
Abstract: The adipose-derived stem cell exosomes are subcellular structures of adipose stem cells. They are nano-sized membrane vesicles that can transport various cell components and act on target cells by paracrine, and they play an important role in the exchanges of substance and information between cells. Scar healing is the commonest way of healing after skin tissue injury. Pathological scar can not only cause movement dysfunction, but also lead to deformity, which affects the appearance of patients and brings life and mental pressure to the patients. In recent years, many researches have shown that the adipose-derived stem cell exosomes contain a variety of bioactive molecules, which play an important role in reducing scar formation and scar-free wound healing, by affecting the proliferation and migration of fibroblasts and the composition of extracellular matrix. This article reviewed the recent literature on the roles and mechanisms of adipose-derived stem cell exosomes in scar formation, and prospected the future application and development of adipose-derived stem cell exosomes in scar treatment.
- Exosomes /
- Cicatrix /
- Fibroblasts /
- Extracellular matrix /
- Adipose-derived stem cells
所有作者均声明不存在利益冲突

HTML全文

参考文献(44)

[1]	OjehN,BharathaA,GaurU,et al.Keloids: current and emerging therapies[J].Scars Burn Heal,2020,6:2059513120940499.DOI: 10.1177/2059513120940499.
[2]	中国整形美容协会瘢痕医学分会.瘢痕早期治疗全国专家共识(2020版)[J].中华烧伤杂志,2021,37(2):113-125.DOI: 10.3760/cma.j.cn501120-20200609-00300.
[3]	LouP,LiuS,XuX,et al.Extracellular vesicle-based therapeutics for the regeneration of chronic wounds: current knowledge and future perspectives[J].Acta Biomater,2021,119:42-56.DOI: 10.1016/j.actbio.2020.11.001.
[4]	DoyleLM,WangMZ.Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis[J].Cells,2019,8(7):727.DOI: 10.3390/cells8070727.
[5]	MaasS,BreakefieldXO,WeaverAM.Extracellular vesicles: unique intercellular delivery vehicles[J].Trends Cell Biol,2017,27(3):172-188.DOI: 10.1016/j.tcb.2016.11.003.
[6]	JuanT,FürthauerM.Biogenesis and function of ESCRT-dependent extracellular vesicles[J].Semin Cell Dev Biol,2018,74:66-77.DOI: 10.1016/j.semcdb.2017.08.022.
[7]	CabralJ,RyanAE,GriffinMD,et al.Extracellular vesicles as modulators of wound healing[J].Adv Drug Deliv Rev,2018,129:394-406.DOI: 10.1016/j.addr.2018.01.018.
[8]	SabolRA,BowlesAC,CôtéA,et al.Therapeutic potential of adipose stem cells[J].Adv Exp Med Biol,2021,1341:15-25.DOI: 10.1007/5584_2018_248.
[9]	O'BrienK,BreyneK,UghettoS,et al.RNA delivery by extracellular vesicles in mammalian cells and its applications[J].Nat Rev Mol Cell Biol,2020,21(10):585-606.DOI: 10.1038/s41580-020-0251-y.
[10]	GurungS,PerocheauD,TouramanidouL,et al.The exosome journey: from biogenesis to uptake and intracellular signalling[J].Cell Commun Signal,2021,19(1):47.DOI: 10.1186/s12964-021-00730-1.
[11]	ReinkeJM,SorgH.Wound repair and regeneration[J].Eur Surg Res,2012,49(1):35-43.DOI: 10.1159/000339613.
[12]	RippaAL,KalabushevaEP,VorotelyakEA.Regeneration of dermis: scarring and cells involved[J].Cells,2019,8(6):607.DOI: 10.3390/cells8060607.
[13]	WangZC,ZhaoWY,CaoY,et al.The roles of inflammation in keloid and hypertrophic scars[J].Front Immunol,2020,11:603187.DOI: 10.3389/fimmu.2020.603187.
[14]	YangJ,LiS,HeL,et al.Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine[J/OL].Burns Trauma,2021,9:tkab020[2022-03-08].https://pubmed.ncbi.nlm.nih.gov/34514006/.DOI: 10.1093/burnst/tkab020.
[15]	Abdu AllahAMK,MohammedKI,FaragAGA,et al.Interleukin-6 serum level and gene polymorphism in keloid patients[J].Cell Mol Biol (Noisy-le-grand),2019,65(5):43-48.
[16]	ChenZ,GaoZ,XiaL,et al.Dysregulation of DPP4-CXCL12 balance by TGF-β1/SMAD pathway promotes CXCR4+ inflammatory cell infiltration in keloid scars[J].J Inflamm Res,2021,14:4169-4180.DOI: 10.2147/JIR.S326385.
[17]	ChenZ,WangZ,JinT,et al.Fibrogenic fibroblast-selective near-infrared phototherapy to control scarring[J].Theranostics,2019,9(23):6797-6808.DOI: 10.7150/thno.36375.
[18]	ZhuZ,HouQ,LiM,et al.Molecular mechanism of myofibroblast formation and strategies for clinical drugs treatments in hypertrophic scars[J].J Cell Physiol,2020,235(5):4109-4119.DOI: 10.1002/jcp.29302.
[19]	HsuCK,LinHH,HarnHI,et al.Caveolin-1 controls hyperresponsiveness to mechanical stimuli and fibrogenesis-associated RUNX2 activation in keloid fibroblasts[J].J Invest Dermatol,2018,138(1):208-218.DOI: 10.1016/j.jid.2017.05.041.
[20]	YinJL,WuY,YuanZW,et al.Advances in scarless foetal wound healing and prospects for scar reduction in adults[J].Cell Prolif,2020,53(11):e12916.DOI: 10.1111/cpr.12916.
[21]	LeungA,CrombleholmeTM,KeswaniSG.Fetal wound healing: implications for minimal scar formation[J].Curr Opin Pediatr,2012,24(3):371-378.DOI: 10.1097/MOP.0b013e3283535790.
[22]	KavasiRM,BerdiakiA,SpyridakiI,et al.HA metabolism in skin homeostasis and inflammatory disease[J].Food Chem Toxicol,2017,101:128-138.DOI: 10.1016/j.fct.2017.01.012.
[23]	IlieșRF,AioaneiCS,CătanăA,et al.Involvement of COL5A2 and TGF-β1 in pathological scarring[J].Exp Ther Med,2021,22(4):1067.DOI: 10.3892/etm.2021.10501.
[24]	YuanR,DaiX,LiY,et al.Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-β2/Smad3 signaling[J].Mol Med Rep,2021,24(5):758.DOI: 10.3892/mmr.2021.12398.
[25]	LichtmanMK,Otero-VinasM,FalangaV.Transforming growth factor beta (TGF-β) isoforms in wound healing and fibrosis[J].Wound Repair Regen,2016,24(2):215-222.DOI: 10.1111/wrr.12398.
[26]	WalravenM,TalhoutW,BeelenRH,et al.Healthy human second-trimester fetal skin is deficient in leukocytes and associated homing chemokines[J].Wound Repair Regen,2016,24(3):533-541.DOI: 10.1111/wrr.12421.
[27]	MascharakS,desJardins-ParkHE,DavittMF,et al.Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring[J].Science,2021,372(6540):eaba2374.DOI: 10.1126/science.aba2374.
[28]	XuX, GuS, HuangX, et al. The role of macrophages in the formation of hypertrophic scars and keloids[J/OL]. Burns Trauma, 2020,8:tkaa006[2022-03-08]. https://pubmed.ncbi.nlm.nih.gov/32341919/.DOI: 10.1093/burnst/tkaa006.
[29]	HeoJS,ChoiY,KimHO.Adipose-derived mesenchymal stem cells promote M2 macrophage phenotype through exosomes[J].Stem Cells Int,2019,2019:7921760.DOI: 10.1155/2019/7921760.
[30]	DomenisR,CifùA,QuagliaS,et al.Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes[J].Sci Rep,2018,8(1):13325.DOI: 10.1038/s41598-018-31707-9.
[31]	BlazquezR,Sanchez-MargalloFM,de la RosaO,et al.Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells[J].Front Immunol,2014,5:556.DOI: 10.3389/fimmu.2014.00556.
[32]	MaX,ChenJ,XuB,et al.Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro[J].Int J Mol Med,2015,35(5):1246-1256.DOI: 10.3892/ijmm.2015.2135.
[33]	BaiY,HanYD,YanXL,et al.Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury[J].Biochem Biophys Res Commun,2018,500(2):310-317.DOI: 10.1016/j.bbrc.2018.04.065.
[34]	LiangX,ZhangL,WangS,et al.Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a[J].J Cell Sci,2016,129(11):2182-2189.DOI: 10.1242/jcs.170373.
[35]	LiY,ZhangJ,ShiJ,et al.Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis[J].Stem Cell Res Ther,2021,12(1):221.DOI: 10.1186/s13287-021-02290-0.
[36]	WangL,HuL,ZhouX,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.DOI: 10.1038/s41598-017-12919-x.
[37]	LiuJ,LiF,LiuB,et al.Adipose-derived mesenchymal stem cell exosomes inhibit transforming growth factor-β1-induced collagen synthesis in oral mucosal fibroblasts[J].Exp Ther Med,2021,22(6):1419.DOI: 10.3892/etm.2021.10854.
[38]	LiX,WangY,ShiL,et al.Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes[J].J Nanobiotechnology,2020,18(1):113.DOI: 10.1186/s12951-020-00670-x.
[39]	WangC,WangM,XuT,et al.Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration[J].Theranostics,2019,9(1):65-76.DOI: 10.7150/thno.29766.
[40]	WangM,WangC,ChenM,et al.Efficient angiogenesis-based diabetic wound healing/skin reconstruction through bioactive antibacterial adhesive ultraviolet shielding nanodressing with exosome release[J].ACS Nano,2019,13(9):10279-10293.DOI: 10.1021/acsnano.9b03656.
[41]	ZhaoD,YuZ,LiY,et al.GelMA combined with sustained release of HUVECs derived exosomes for promoting cutaneous wound healing and facilitating skin regeneration[J].J Mol Histol,2020,51(3):251-263.DOI: 10.1007/s10735-020-09877-6.
[42]	SafariB,AghazadehM,DavaranS,et al.Exosome-loaded hydrogels: a new cell-free therapeutic approach for skin regeneration[J].Eur J Pharm Biopharm,2022,171:50-59.DOI: 10.1016/j.ejpb.2021.11.002.
[43]	ElsharkasyOM,NordinJZ,HageyDW,et al.Extracellular vesicles as drug delivery systems: why and how?[J].Adv Drug Deliv Rev,2020,159:332-343.DOI: 10.1016/j.addr.2020.04.004.
[44]	LvQ, DengJ, ChenY, 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):1723-1733.DOI: 10.1021/acs.molpharmaceut.0c00177.