Research advances on exosomes derived from adipose-derived mesenchymal stem cells in promoting diabetic wound healing
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摘要:
糖尿病创面形成的病理机制是导致糖尿病创面愈合困难的重要原因之一，难愈的糖尿病创面为患者及社会带来沉重负担。来源于干细胞的外泌体具有与干细胞相似的促组织再生能力及更多的临床优势，逐渐在创面愈合中发挥重要作用。近年来，诸多研究显示，脂肪间充质干细胞外泌体（ADSC-EXO）通过参与糖尿病创面愈合的各个过程，促进创面愈合。该文就导致糖尿病创面愈合困难的病理机制、ADSC-EXO促进糖尿病创面愈合的相关作用机制及其应用前景进行综述。
Abstract:Impaired healing of diabetic wounds is mainly attributed to its pathological mechanism, and refractory diabetic wounds bring heavy burdens to patients and society. Exosomes derived from stem cells possess the similar ability as stem cells in promoting tissue regeneration and more clinical advantages and are gradually playing important roles in wound healing. In recent years, researches have shown that exosomes derived from adipose-derived mesenchymal stem cells (ADSC-EXOs) can promote the healing of diabetic wounds by participating in various processes of wound healing. This article reviews the pathological mechanism leading to impaired healing of diabetic wounds, the related mechanism and the application prospect of ADSC-EXOs in promoting diabetic wound healing.
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Key words:
- Diabetes mellitus /
- Wound healing /
- Exosomes /
- Adipose-derived mesenchymal stem cells
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所有作者均声明不存在利益冲突
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参考文献
(45) [1] SaeediP,PetersohnI,SalpeaP,et al.Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition[J].Diabetes Res Clin Pract,2019,157:107843.DOI: 10.1016/j.diabres.2019.107843. [2] WalshJW,HoffstadOJ,SullivanMO,et al.Association of diabetic foot ulcer and death in a population-based cohort from the United Kingdom[J].Diabet Med,2016,33(11):1493-1498.DOI: 10.1111/dme.13054. [3] 海峡两岸医药卫生交流协会烧创伤暨组织修复专委会. 负压伤口疗法在糖尿病足创面治疗中的应用全国专家共识(2021版) [J] . 中华烧伤杂志, 2021, 37(6): 508-518. DOI: 10.3760/cma.j.cn501120-20210107-00010. [4] Nourian DehkordiA, Mirahmadi BabaheydariF, ChehelgerdiM, et al. Skin tissue engineering: wound healing based on stem-cell-based therapeutic strategies[J]. Stem Cell Res Ther, 2019, 10(1): 111. DOI: 10.1186/s13287-019-1212-2. [5] QiuX, LiuJ, ZhengC, et al. Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis[J]. Cell Prolif, 2020, 53(8): e12830. DOI: 10.1111/cpr.12830. [6] WolfDA,BeesonW,RachelJD,et al.Mesothelial stem cells and stromal vascular fraction for skin rejuvenation[J].Facial Plast Surg Clin North Am,2018,26(4):513-532.DOI: 10.1016/j.fsc.2018.06.011. [7] TrounsonA,McDonaldC.Stem cell therapies in clinical trials: progress and challenges[J].Cell Stem Cell,2015,17(1):11-22.DOI: 10.1016/j.stem.2015.06.007. [8] SwaminathanM,Stafford-SmithM,ChertowGM,et al.Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery[J].J Am Soc Nephrol,2018,29(1):260-267.DOI: 10.1681/ASN.2016101150. [9] WangA, LvG, ChengX, et al. Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition)[J/OL]. Burns Trauma, 2020,8:tkaa017[2021-02-18]. https://pubmed.ncbi.nlm.nih.gov/32685563/. DOI: 10.1093/burnst/tkaa017. [10] ParkJH,HwangI,HwangSH,et al.Human umbilical cord blood-derived mesenchymal stem cells prevent diabetic renal injury through paracrine action[J].Diabetes Res Clin Pract,2012,98(3):465-473.DOI: 10.1016/j.diabres.2012.09.034. [11] KowalJ,ArrasG,ColomboM,et al.Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes[J].Proc Natl Acad Sci U S A,2016,113(8):E968-977.DOI: 10.1073/pnas.1521230113. [12] Varderidou-MinasianS,LorenowiczMJ.Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities[J].Theranostics,2020,10(13):5979-5997.DOI: 10.7150/thno.40122. [13] TavernaS,PucciM,AlessandroR.Extracellular vesicles: small bricks for tissue repair/regeneration[J].Ann Transl Med,2017,5(4):83.DOI: 10.21037/atm.2017.01.53. [14] BaumCL,ArpeyCJ.Normal cutaneous wound healing: clinical correlation with cellular and molecular events[J].Dermatol Surg,2005,31(6):674-686; discussion 686.DOI: 10.1111/j.1524-4725.2005.31612. [15] MouraJ,MadureiraP,LealEC,et al.Immune aging in diabetes and its implications in wound healing[J].Clin Immunol,2019,200:43-54.DOI: 10.1016/j.clim.2019.02.002. [16] MirzaRE,FangMM,NovakML,et al.Macrophage PPARγ and impaired wound healing in type 2 diabetes[J].J Pathol,2015,236(4):433-444.DOI: 10.1002/path.4548. [17] Basu MallikS,JayashreeBS,ShenoyRR.Epigenetic modulation of macrophage polarization-perspectives in diabetic wounds[J].J Diabetes Complications,2018,32(5):524-530.DOI: 10.1016/j.jdiacomp.2018.01.015. [18] KathawalaMH,NgWL,LiuD,et al.Healing of chronic wounds: an update of recent developments and future possibilities[J].Tissue Eng Part B Rev,2019,25(5):429-444.DOI: 10.1089/ten.TEB.2019.0019. [19] OkonkwoUA,DiPietroLA.Diabetes and wound angiogenesis[J].Int J Mol Sci,2017,18(7):1419.DOI: 10.3390/ijms18071419. [20] den DekkerA,DavisFM,KunkelSL,et al.Targeting epigenetic mechanisms in diabetic wound healing[J].Transl Res,2019,204:39-50.DOI: 10.1016/j.trsl.2018.10.001. [21] ForresterSJ,KikuchiDS,HernandesMS,et al.Reactive oxygen species in metabolic and inflammatory signaling[J].Circ Res,2018,122(6):877-902.DOI: 10.1161/CIRCRESAHA.117.311401. [22] CatrinaSB,ZhengX.Disturbed hypoxic responses as a pathogenic mechanism of diabetic foot ulcers[J].Diabetes Metab Res Rev,2016,32 Suppl 1:S179-185.DOI: 10.1002/dmrr.2742. [23] RohaniMG,ParksWC.Matrix remodeling by MMPs during wound repair[J].Matrix Biol,2015,44-46:113-121.DOI: 10.1016/j.matbio.2015.03.002. [24] JonesJI,NguyenTT,PengZ,et al.Targeting MMP-9 in diabetic foot ulcers[J].Pharmaceuticals (Basel),2019,12(2):79.DOI: 10.3390/ph12020079. [25] ZhaoH,ShangQ,PanZ,et al.Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue[J].Diabetes,2018,67(2):235-247.DOI: 10.2337/db17-0356. [26] LiX,XieX,LianW,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):1-14.DOI: 10.1038/s12276-018-0058-5. [27] LiuW,LiL,RongY,et al.Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126[J].Acta Biomater,2020,103:196-212.DOI: 10.1016/j.actbio.2019.12.020. [28] HuP,YangQ,WangQ,et al.Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration[J/OL].Burns Trauma,2019,7:38[2021-02-18]. https://pubmed.ncbi.nlm.nih.gov/31890717/. DOI: 10.1186/s41038-019-0178-8. [29] ZhuLL,HuangX,YuW,et al.Transplantation of adipose tissue-derived stem cell-derived exosomes ameliorates erectile function in diabetic rats[J].Andrologia,2018,50(2):e12871. DOI: 10.1111/and.12871. [30] RenS,ChenJ,DuscherD,et al.Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways[J].Stem Cell Res Ther,2019,10(1):47.DOI: 10.1186/s13287-019-1152-x. [31] XueC,ShenY,LiX,et al.Exosomes derived from hypoxia-treated human adipose mesenchymal stem cells enhance angiogenesis through the PKA signaling pathway[J].Stem Cells Dev,2018,27(7):456-465.DOI: 10.1089/scd.2017.0296. [32] HanY,RenJ,BaiY,et al.Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R[J].Int J Biochem Cell Biol,2019,109:59-68.DOI: 10.1016/j.biocel.2019.01.017. [33] YangY,CaiY,ZhangY,et al.Exosomes secreted by adipose-derived stem cells contribute to angiogenesis of brain microvascular endothelial cells following oxygen-glucose deprivation in vitro through microRNA-181b/TRPM7 axis[J].J Mol Neurosci,2018,65(1):74-83.DOI: 10.1007/s12031-018-1071-9. [34] MaT,FuB,YangX,et al.Adipose mesenchymal stem cell-derived exosomes promote cell proliferation, migration, and inhibit cell apoptosis via Wnt/β-catenin signaling in cutaneous wound healing[J].J Cell Biochem,2019,120(6):10847-10854.DOI: 10.1002/jcb.28376. [35] ZhangW,BaiX,ZhaoB,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):333-342.DOI: 10.1016/j.yexcr.2018.06.035. [36] ShiekhPA,SinghA,KumarA.Exosome laden oxygen releasing antioxidant and antibacterial cryogel wound dressing OxOBand alleviate diabetic and infectious wound healing[J].Biomaterials,2020,249:120020.DOI: 10.1016/j.biomaterials.2020.120020. [37] ChoiEW,SeoMK,WooEY,et al.Exosomes from human adipose-derived stem cells promote proliferation and migration of skin fibroblasts[J].Exp Dermatol,2018,27(10):1170-1172.DOI: 10.1111/exd.13451. [38] 王江文,易阳艳,朱元正,等.脂肪干细胞来源外泌体促进糖尿病小鼠创面愈合的实验研究[J].中国修复重建外科杂志,2020,34(1):124-131.DOI: 10.7507/1002-1892.201903058. [39] 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. [40] 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. [41] 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. [42] YangC,LuoL,BaiX,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.DOI: 10.1016/j.abb.2020.108259. [43] LuZ,ChenY,DunstanC,et al.Priming adipose stem cells with tumor necrosis factor-alpha preconditioning potentiates their exosome efficacy for bone regeneration[J].Tissue Eng Part A,2017,23(21/22):1212-1220.DOI: 10.1089/ten.tea.2016.0548. [44] QuY,ZhangQ,CaiX,et al.Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation[J].J Cell Mol Med,2017,21(10):2491-2502.DOI: 10.1111/jcmm.13170. [45] WangX,GuH,HuangW,et al.Hsp20-mediated activation of exosome biogenesis in cardiomyocytes improves cardiac function and angiogenesis in diabetic mice[J].Diabetes,2016,65(10):3111-3128.DOI: 10.2337/db15-1563. 期刊类型引用(8)
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