间充质干细胞来源细胞外囊泡促进糖尿病溃疡血管生成的研究进展

刘文剑; 刘德伍

doi:10.3760/cma.j.cn501120-20201207-00520

间充质干细胞来源细胞外囊泡促进糖尿病溃疡血管生成的研究进展

doi: 10.3760/cma.j.cn501120-20201207-00520

刘文剑,
刘德伍^,

1.
武警江西总队医院烧伤整形科，南昌　　330030
2.
南昌大学第一附属医院烧伤科，南昌　　330006

基金项目:

国家自然科学基金地区科学基金项目 81460293

详细信息

通讯作者:
刘德伍，Email：dewuliu@126.com

计量
- 文章访问数: 532
- HTML全文浏览量: 102
- PDF下载量: 40
- 被引次数: 0
出版历程
- 收稿日期: 2020-12-07

Research advances on mesenchymal stem cell-derived extracellular vesicles in promoting angiogenesis of diabetic ulcers

Liu Wenjian,
Liu Dewu^,

1.
Department of Burns and Plastic Surgery, Jiangxi General Hospital of Armed Police, Nanchang 330030,China
2.
Department of Burns, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China

Funds:

Regional Science Foundation Project of National Natural Science Foundation of China 81460293

More Information

Corresponding author: Liu Dewu, Email: dewuliu@126.com

摘要

摘要: 细胞外囊泡（EV）是大多数真核细胞分泌的纳米级颗粒，在细胞间的物质转运和信息传递中扮演重要角色，参与炎症、血管生成、抗原呈递、细胞凋亡及分化等生物学过程。间充质干细胞（MSC）培养上清液中富含EV，EV可调控创面愈合和组织修复的关键步骤——新血管形成，而糖尿病溃疡迁延不愈与创面血管网络的形成受阻密切相关。该文就MSC来源EV在促进糖尿病溃疡血管生成中的作用进行综述，以期为糖尿病溃疡治疗提供一种新思路。
- 糖尿病 /
- 伤口愈合 /
- 间质干细胞 /
- 外泌体 /
- 细胞外囊泡 /
- 血管新生
Abstract: Extracellular vesicles are nanoparticles secreted by most eukaryotic cells and play important roles in material transport and information transmission between cells, involved in inflammation, angiogenesis, antigen presentation, cell apoptosis, cell differentiation, and other biological processes. The culture supernatant of mesenchymal stem cells is rich in extracellular vesicles, and the extracellular vesicles can regulate the formation of new blood vessels, a key step in wound healing and tissue repair. The persistence of diabetic ulcers is closely related to the blocked formation of wound vascular network. This article reviews the role of extracellular vesicles derived from mesenchymal stem cells in promoting angiogenesis of diabetic ulcers, in order to provide a new idea for the treatment of diabetic ulcers.
- Diabetes mellitus /
- Wound healing /
- Mesenchymal stem cells /
- Exosomes /
- Extracellular vesicles /
- Angiogenesis
所有作者均声明不存在利益冲突

HTML全文

参考文献(68)

[1]	ChengL,ZhangK,WuS,et al.Focus on mesenchymal stem cell-derived exosomes: opportunities and challenges in cell-free therapy[J].Stem Cells Int,2017,2017:6305295.DOI: 10.1155/2017/6305295.
[2]	魏在荣,王达利.间充质干细胞与创面修复——间充质干细胞微环境细胞外囊泡假说[J].中华整形外科杂志,2019,35(4):324-330.DOI: 10.3760/cma.j.issn.1009-4598.2019.04.002.
[3]	MartinP.Wound healing--aiming for perfect skin regeneration[J].Science,1997,276(5309):75-81.DOI: 10.1126/science.276.5309.75.
[4]	PanBT,JohnstoneRM.Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor[J].Cell,1983,33(3):967-978.DOI: 10.1016/0092-8674(83)90040-5.
[5]	HardingC,HeuserJ,StahlP.Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding[J].Eur J Cell Biol,1984,35(2):256-263.
[6]	JohnstoneRM,BianchiniA,TengK.Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions[J].Blood,1989,74(5):1844-1851.
[7]	RaniS,RyanAE,GriffinMD,et al.Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications[J].Mol Ther,2015,23(5):812-823.DOI: 10.1038/mt.2015.44.
[8]	KalraH,DrummenGP,MathivananS.Focus on extracellular vesicles: introducing the next small big thing[J].Int J Mol Sci,2016,17(2):170.DOI: 10.3390/ijms17020170.
[9]	ThéryC,WitwerKW,AikawaE,et al.Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines[J].J Extracell Vesicles,2018,7(1):1535750.DOI: 10.1080/20013078.2018.1535750.
[10]	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-e977.DOI: 10.1073/pnas.1521230113.
[11]	SkotlandT,SandvigK,LlorenteA.Lipids in exosomes: current knowledge and the way forward[J].Prog Lipid Res,2017,66:30-41.DOI: 10.1016/j.plipres.2017.03.001.
[12]	TkachM,ThéryC.Communication by extracellular vesicles: where we are and where we need to go[J].Cell,2016,164(6):1226-1232.DOI: 10.1016/j.cell.2016.01.043.
[13]	DorayappanK,WallbillichJJ,CohnDE,et al.The biological significance and clinical applications of exosomes in ovarian cancer[J].Gynecol Oncol,2016,142(1):199-205.DOI: 10.1016/j.ygyno.2016.03.036.
[14]	Ramos TL,Sánchez-AbarcaLI,MuntiónS,et al.MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry[J].Cell Commun Signal,2016,14:2.DOI: 10.1186/s12964-015-0124-8.
[15]	AndersonJD,JohanssonHJ,GrahamCS,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):601-613.DOI: 10.1002/stem.2298.
[16]	YamashitaT,TakahashiY,TakakuraY.Possibility of exosome-based therapeutics and challenges in production of exosomes eligible for therapeutic application[J].Biol Pharm Bull,2018,41(6):835-842.DOI: 10.1248/bpb.b18-00133.
[17]	MoonKC,SuhHS,KimKB,et al.Potential of allogeneic adipose-derived stem cell-hydrogel complex for treating diabetic foot ulcers[J].Diabetes,2019,68(4):837-846.DOI: 10.2337/db18-0699.
[18]	WuP,ZhangB,ShiH,et al.MSC-exosome: a novel cell-free therapy for cutaneous regeneration[J].Cytotherapy,2018,20(3):291-301.DOI: 10.1016/j.jcyt.2017.11.002.
[19]	RocheS, D'IppolitoG, GomezLA,et al.Comparative analysis of protein expression of three stem cell populations: models of cytokine delivery system in vivo[J].Int J Pharm,2013,440(1):72-82.DOI: 10.1016/j.ijpharm.2011.12.041.
[20]	ThanU,GuanzonD,LeavesleyD,et al.Association of extracellular membrane vesicles with cutaneous wound healing[J].Int J Mol Sci,2017,18(5):956.DOI: 10.3390/ijms18050956.
[21]	KusumaGD,CarthewJ,LimR,et al.Effect of the microenvironment on mesenchymal stem cell paracrine signaling: opportunities to engineer the therapeutic effect[J].Stem Cells Dev,2017,26(9):617-631.DOI: 10.1089/scd.2016.0349.
[22]	AndersonJD,JohanssonHJ,GrahamCS,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):601-613.DOI: 10.1002/stem.2298.
[23]	CamussiG,DeregibusMC,BrunoS,et al.Exosomes/microvesicles as a mechanism of cell-to-cell communication[J].Kidney Int,2010,78(9):838-848.DOI: 10.1038/ki.2010.278.
[24]	Yáñez-MóM,SiljanderPR,AndreuZ,et al.Biological properties of extracellular vesicles and their physiological functions[J].J Extracell Vesicles,2015,4:27066.DOI: 10.3402/jev.v4.27066.
[25]	Demidova-RiceTN,DurhamJT,HermanIM.Wound healing angiogenesis: innovations and challenges in acute and chronic wound healing[J].Adv Wound Care (New Rochelle),2012,1(1):17-22.DOI: 10.1089/wound.2011.0308.
[26]	TandaraAA,MustoeTA.Oxygen in wound healing--more than a nutrient[J].World J Surg,2004,28(3):294-300.DOI: 10.1007/s00268-003-7400-2.
[27]	MoleDR,BlancherC,CopleyRR,et al.Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts[J].J Biol Chem,2009,284(25):16767-16775.DOI: 10.1074/jbc.M901790200.
[28]	唐黎珺,张筱薇,金俊俊,等.脂肪源性间充质干细胞外泌体在慢性创面治疗中作用机制的研究进展[J].中华烧伤杂志,2021,37(2):191-195.DOI: 10.3760/cma.j.cn501120-20200220-00076.
[29]	TsaiHW,WangPH,TsuiKH.Mesenchymal stem cell in wound healing and regeneration[J].J Chin Med Assoc,2018,81(3):223-224.DOI: 10.1016/j.jcma.2017.06.011.
[30]	MartinPE, O'ShaughnessyEM, WrightCS,et al.The potential of human induced pluripotent stem cells for modelling diabetic wound healing in vitro[J].Clin Sci (Lond),2018,132(15):1629-1643.DOI: 10.1042/CS20171483.
[31]	KimYH,TabataY.Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure[J].J Biomed Mater Res A,2016,104(4):942-956.DOI: 10.1002/jbm.a.35635.
[32]	KhannaS,BiswasS,ShangY,et al.Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice[J].PLoS One,2010,5(3):e9539.DOI: 10.1371/journal.pone.0009539.
[33]	SteinleH,GolombekS,BehringA,et al.Improving the angiogenic potential of EPCs via engineering with synthetic modified mRNAs[J].Mol Ther Nucleic Acids,2018,13:387-398.DOI: 10.1016/j.omtn.2018.09.005.
[34]	El-BahyA,AboulmagdYM,ZakiM.Diabetex: a novel approach for diabetic wound healing[J].Life Sci,2018,207:332-339.DOI: 10.1016/j.lfs.2018.06.020.
[35]	QiW,YangC,DaiZ,et al.High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling[J].Diabetes,2015,64(4):1407-1419.DOI: 10.2337/db14-1111.
[36]	Otero-ViñasM,FalangaV.Mesenchymal stem cells in chronic wounds: the spectrum from basic to advanced therapy[J].Adv Wound Care (New Rochelle),2016,5(4):149-163.DOI: 10.1089/wound.2015.0627.
[37]	LaiRC,ChenTS,LimSK.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.
[38]	LiX,JiangC,ZhaoJ.Human endothelial progenitor cells-derived exosomes accelerate cutaneous wound healing in diabetic rats by promoting endothelial function[J].J Diabetes Complications,2016,30(6):986-992.DOI: 10.1016/j.jdiacomp.2016.05.009.
[39]	FridoniM,KouhkheilR,AbdollhifarMA,et al.Improvement in infected wound healing in type 1 diabetic rat by the synergistic effect of photobiomodulation therapy and conditioned medium[J].J Cell Biochem,2019,120(6):9906-9916.DOI: 10.1002/jcb.28273.
[40]	ShabbirA,CoxA,Rodriguez-MenocalL,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.
[41]	BoraP,MajumdarAS.Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation[J].Stem Cell Res Ther,2017,8(1):145.DOI: 10.1186/s13287-017-0598-y.
[42]	GadelkarimM,AbushoukAI,GhanemE,et al.Adipose-derived stem cells: effectiveness and advances in delivery in diabetic wound healing[J].Biomed Pharmacother,2018,107:625-633.DOI: 10.1016/j.biopha.2018.08.013.
[43]	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.
[44]	BakhtyarN,JeschkeMG,HererE,et al.Exosomes from acellular Wharton's jelly of the human umbilical cord promotes skin wound healing[J].Stem Cell Res Ther,2018,9(1):193.DOI: 10.1186/s13287-018-0921-2.
[45]	ShiQ,QianZ,LiuD,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.DOI: 10.3389/fphys.2017.00904.
[46]	KatsudaT,OchiyaT.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.
[47]	PetkovicM,SørensenAE,LealEC,et al.Mechanistic actions of microRNAs in diabetic wound healing[J].Cells,2020, 9(10):2228. DOI: 10.3390/cells9102228.
[48]	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.
[49]	KangT,JonesTM,NaddellC,et al.Adipose-derived stem cells induce angiogenesis via microvesicle transport of miRNA-31[J].Stem Cells Transl Med,2016,5(4):440-450.DOI: 10.5966/sctm.2015-0177.
[50]	ZhangD,LiZ,WangZ,et al.MicroRNA-126: a promising biomarker for angiogenesis of diabetic wounds treated with negative pressure wound therapy[J].Diabetes Metab Syndr Obes,2019,12:1685-1696.DOI: 10.2147/DMSO.S199705.
[51]	TaoSC,GuoSC,LiM,et al.Chitosan wound dressings incorporating exosomes derived from microRNA-126-overexpressing synovium mesenchymal stem cells provide sustained release of exosomes and heal full-thickness skin defects in a diabetic rat model[J].Stem Cells Transl Med,2017,6(3):736-747.DOI: 10.5966/sctm.2016-0275.
[52]	XuJ,BaiS,CaoY,et al.miRNA-221-3p in endothelial progenitor cell-derived exosomes accelerates skin wound healing in diabetic mice[J].Diabetes Metab Syndr Obes,2020,13:1259-1270.DOI: 10.2147/DMSO.S243549.
[53]	YuP,GuoJ,LiJ,et al.Co-expression network analysis revealing the key lncRNAs in diabetic foot ulcers[J].Arch Med Sci,2019,15(5):1123-1132.DOI: 10.5114/aoms.2019.84699.
[54]	YuT,GaoM,YangP,et al.Insulin promotes macrophage phenotype transition through PI3K/Akt and PPAR-γ signaling during diabetic wound healing[J].J Cell Physiol,2019,234(4):4217-4231.DOI: 10.1002/jcp.27185.
[55]	TaoSC,RuiBY,WangQY,et al.Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds[J].Drug Deliv,2018,25(1):241-255.DOI: 10.1080/10717544.2018.1425774.
[56]	LiB,LuanS,ChenJ,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.
[57]	HeL,ZhuC,JiaJ,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.DOI: 10.1042/BSR20192549.
[58]	AbdulleLE,HaoJL,PantOP,et al.MALAT1 as a diagnostic and therapeutic target in diabetes-related complications: a promising long-noncoding RNA[J].Int J Med Sci,2019,16(4):548-555.DOI: 10.7150/ijms.30097.
[59]	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.
[60]	Gonzalez-KingH,GarcíaNA,Ontoria-OviedoI,et al.Hypoxia inducible factor-1α potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes[J].Stem Cells,2017,35(7):1747-1759.DOI: 10.1002/stem.2618.
[61]	AnSY,HanJ,LimHJ,et al.Valproic acid promotes differentiation of hepatocyte-like cells from whole human umbilical cord-derived mesenchymal stem cells[J].Tissue Cell,2014,46(2):127-135.DOI: 10.1016/j.tice.2013.12.006.
[62]	DingJ,WangX,ChenB,et al.Exosomes derived from human bone marrow mesenchymal stem cells stimulated by deferoxamine accelerate cutaneous wound healing by promoting angiogenesis[J].Biomed Res Int,2019,2019:9742765.DOI: 10.1155/2019/9742765.
[63]	AriyantiAD,ZhangJ,MarcelinaO,et al.Salidroside-pretreated mesenchymal stem cells enhance diabetic wound healing by promoting paracrine function and survival of mesenchymal stem cells under hyperglycemia[J].Stem Cells Transl Med,2019,8(4):404-414.DOI: 10.1002/sctm.18-0143.
[64]	HuY,TaoR,ChenL,et al.Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis[J].J Nanobiotechnology,2021,19(1):150.DOI: 10.1186/s12951-021-00894-5.
[65]	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.
[66]	DuW,ZhangK,ZhangS,et al.Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer[J].Biomaterials,2017,133:70-81.DOI: 10.1016/j.biomaterials.2017.04.030.
[67]	RafiqQA,CoopmanK,NienowAW,et al.Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors[J].Biotechnol J,2016,11(4):473-486.DOI: 10.1002/biot.201400862.
[68]	KalluriR, LeBleuVS. The biology, function, and biomedical applications of exosomes[J]. Science,2020,367(6478):eaau6977. DOI: 10.1126/science.aau6977.