提高间充质干细胞外泌体创面修复疗效的研究进展

段育任; 赵雨晨; 宋文禹; 王佳欣; 裴洁; 王小兵

doi:10.3760/cma.j.cn501225-20220912-00402

提高间充质干细胞外泌体创面修复疗效的研究进展

doi: 10.3760/cma.j.cn501225-20220912-00402

1.
山西医科大学第一医院烧伤整形科，太原　　030001
2.
咸阳市中心医院烧伤整形科，咸阳　　712099
3.
山西白求恩医院（山西医学科学院　同济山西医院），山西医科大学第三医院整形外科，太原　　030032

基金项目:

山西省基础研究计划青年科学研究项目 202103021223412

详细信息

通讯作者:
王小兵，Email：xiaobingw1970@163.com

计量
- 文章访问数: 203
- HTML全文浏览量: 48
- PDF下载量: 39
- 被引次数: 0
出版历程
- 收稿日期: 2022-09-12
- 网络出版日期: 2023-07-19

Research advances on improving the therapeutic efficacy of mesenchymal stem cell-derived exosomes in wound repair

1.
Department of Burns and Plastic Surgery, the First Hospital of Shanxi Medical University, Taiyuan 030001, China
2.
Department of Burns and Plastic Surgery, Xianyang Central Hospital, Xianyang 712099, China
3.
Department of Plastic Surgery, Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital), the Third Hospital of Shanxi Medical University, Taiyuan 030032, China

Funds:

Shanxi Provincial Basic Research Program Youth Science Research Project 202103021223412

More Information

Corresponding author: Wang Xiaobing, Email: xiaobingw1970@163.com

摘要

摘要: 如何促进创面高质量愈合是整形外科和烧伤科医师共同面临的问题。近年来，大量动物研究表明间充质干细胞外泌体通过多种机制促进创面修复，是具有广阔应用前景的无细胞治疗剂。如何强化外泌体治疗效力、优化其给药策略、改善其生物性能，是外泌体治疗创面从基础研究推向临床应用所需攻克的难关。该文着重探讨提高间充质干细胞外泌体创面修复潜力的方法，从预处理亲本间充质干细胞、水凝胶生物支架装载外泌体、工程化外泌体3个方面综述了近年来提高间充质干细胞外泌体创面修复疗效的研究进展，为后续临床研究提供参考。
- 间充质干细胞 /
- 外泌体 /
- 水凝胶 /
- 创面修复
Abstract: How to promote high-quality wound healing is a common problem for plastic surgery and burn physicians. In recent years, numerous animal studies have demonstrated that mesenchymal stem cell-derived exosomes promote wound repair through multiple mechanisms and are promising cell-free therapeutic agents with broad prospect of application. How to enhance the therapeutic efficacy of exosomes, optimize their drug delivery strategy, and improve their biological properties are the challenges to be overcome in order to move from basic research to clinical application of exosome therapy for wound repair. This article focuses on methods to improve the wound repair potential of mesenchymal stem cell-derived exosomes, and reviews the recent research advances on improving the therapeutic efficacy of mesenchymal stem cell-derived exosomes in wound repair from three aspects, including pretreatment of parental mesenchymal stem cells, hydrogel bio-scaffold loaded with exosomes, and engineered exosomes, to provide a reference for further clinical studies.
- Mesenchymal stem cells /
- Exosomes /
- Hydrogel /
- Wound repair
所有作者均声明不存在利益冲突

HTML全文

参考文献(40)

[1]	ZakeriA,KhasebS,Akhavan RahnamaM,et al.Exosomes derived from mesenchymal stem cells: a promising cell-free therapeutic tool for cutaneous wound healing[J].Biochimie,2023,209:73-84.DOI: 10.1016/j.biochi.2023.01.013.
[2]	HuP,YangQX,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[2022-09-12].https://pubmed.ncbi.nlm.nih.gov/31890717/.DOI: 10.1186/s41038-019-0178-8.
[3]	BianDH,WuY,SongGD,et al.The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review[J].Stem Cell Res Ther,2022,13(1):24.DOI: 10.1186/s13287-021-02697-9.
[4]	ZhangB,WuXD,ZhangX,et al.Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/β-catenin pathway[J].Stem Cells Transl Med,2015,4(5):513-522.DOI: 10.5966/sctm.2014-0267.
[5]	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.
[6]	HuL,WangJ,ZhouX,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.DOI: 10.1038/srep32993.
[7]	TiDD,HaoHJ,TongC,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.DOI: 10.1186/s12967-015-0642-6.
[8]	LiuW,YuMY,XieD,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.DOI: 10.1186/s13287-020-01756-x.
[9]	HuYQ,TaoRY,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.
[10]	YuMY,LiuW,LiJX,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.DOI: 10.1186/s13287-020-01824-2.
[11]	DingJN, 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.
[12]	PendseS, KaleV, VaidyaA. Extracellular vesicles isolated from mesenchymal stromal cells primed with hypoxia: novel strategy in regenerative medicine[J]. Curr Stem Cell Res Ther,2021,16(3):243-261.DOI: 10.2174/1574888X15999200918110638.
[13]	DongJ, WuB, TianW. Exosomes derived from hypoxia-preconditioned mesenchymal stem cells (hypoMSCs-Exo): advantages in disease treatment[J]. Cell Tissue Res,2023,392(3):621-629. DOI: 10.1007/s00441-023-03758-6.
[14]	ZhangXF,WangT,WangZX,et al.Hypoxic ucMSC-secreted exosomal miR-125b promotes endothelial cell survival and migration during wound healing by targeting TP53INP1[J].Mol Ther Nucleic Acids,2021,26:347-359.DOI: 10.1016/j.omtn.2021.07.014.
[15]	WangJ,WuH,PengYX,et al.Hypoxia adipose stem cell-derived exosomes promote high-quality healing of diabetic wound involves activation of PI3K/Akt pathways[J].J Nanobiotechnology,2021,19(1):202.DOI: 10.1186/s12951-021-00942-0.
[16]	Sapir-LekhovitserY,RotenbergMY,JoppJ,et al.Magnetically actuated tissue engineered scaffold: insights into mechanism of physical stimulation[J].Nanoscale,2016,8(6):3386-3399.DOI: 10.1039/c5nr05500h.
[17]	WuD, KangL, TianJJ, et al. Exosomes derived from bone mesenchymal stem cells with the stimulation of Fe3O4 nanoparticles and static magnetic field enhance wound healing through upregulated miR-21-5p[J]. Int J Nanomedicine,2020,15:7979-7993.DOI: 10.2147/IJN.S275650.
[18]	OngWK,ChenHF,TsaiCT,et al.The activation of directional stem cell motility by green light-emitting diode irradiation[J].Biomaterials,2013,34(8):1911-1920.DOI: 10.1016/j.biomaterials.2012.11.065.
[19]	YangK,LiD,WangMT,et al.Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells[J].Stem Cell Res Ther,2019,10(1):358.DOI: 10.1186/s13287-019-1472-x.
[20]	SaparovA, OgayV, NurgozhinT, et al.Preconditioning of human mesen-chymal stem cells to enhance their regulation of the immune response[J]. Stem Cells Int,2016,2016:3924858.DOI: 10.1155/2016/3924858.
[21]	NakaoY,FukudaT,ZhangQZ,et al.Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss[J].Acta Biomater,2021,122:306-324.DOI: 10.1016/j.actbio.2020.12.046.
[22]	PanW,ChenHY,WangAJ,et al.Challenges and strategies: scalable and efficient production of mesenchymal stem cells-derived exosomes for cell-free therapy[J].Life Sci,2023,319:121524.DOI: 10.1016/j.lfs.2023.121524.
[23]	CaoJY,WangB,TangTT,et al.Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury[J].Stem Cell Res Ther,2020,11(1):206.DOI: 10.1186/s13287-020-01719-2.
[24]	YanLT,WuX.Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity[J].Cell Biol Toxicol,2020,36(2):165-178.DOI: 10.1007/s10565-019-09504-5.
[25]	FaruquFN,Liam-OrR,ZhouS,et al.Defined serum-free three-dimensional culture of umbilical cord-derived mesenchymal stem cells yields exosomes that promote fibroblast proliferation and migration in vitro[J].FASEB J,2021,35(1):e21206.DOI: 10.1096/fj.202001768RR.
[26]	FranceskoA,PetkovaP,TzanovT.Hydrogel dressings for advanced wound management[J]. Curr Med Chem,2018,25(41):5782-5797.DOI: 10.2174/0929867324666170920161246.
[27]	ZhouY,ZhangXL,LuST,et al.Human adipose-derived mesenchymal stem cells-derived exosomes encapsulated in pluronic F127 hydrogel promote wound healing and regeneration[J].Stem Cell Res Ther,2022,13(1):407.DOI: 10.1186/s13287-022-02980-3.
[28]	WangCG,WangM,XuTZ,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.
[29]	WangCY,LiangCY,WangR,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):313-324.DOI: 10.1039/c9bm01207a.
[30]	GengXR,QiY,LiuXT,et al.A multifunctional antibacterial and self-healing hydrogel laden with bone marrow mesenchymal stem cell-derived exosomes for accelerating diabetic wound healing[J].Biomater Adv,2022,133:112613.DOI: 10.1016/j.msec.2021.112613.
[31]	ZhangM,ZhaoX.Alginate hydrogel dressings for advanced wound management[J].Int J Biol Macromol,2020,162:1414-1428.DOI: 10.1016/j.ijbiomac.2020.07.311.
[32]	ShafeiS,KhanmohammadiM,HeidariR,et al.Exosome loaded alginate hydrogel promotes tissue regeneration in full-thickness skin wounds: an in vivo study[J].J Biomed Mater Res A,2020,108(3):545-556.DOI: 10.1002/jbm.a.36835.
[33]	MaJ, ZhaoYY, SunL, et al.Exosomes derived from Akt-modified human umbilical cord mesenchymal stem cells improve cardiac regeneration and promote angiogenesis via activating platelet-derived growth factor D[J]. Stem Cells Transl Med,2017,6(1):51-59.DOI: 10.5966/sctm.2016-0038.
[34]	MaJ,ZhangZF,WangYM,et al.Investigation of miR-126-3p loaded on adipose stem cell-derived exosomes for wound healing of full-thickness skin defects[J].Exp Dermatol,2022,31(3):362-374.DOI: 10.1111/exd.14480.
[35]	LiangZH,PanNF,LinSS,et al.Exosomes from mmu_circ_0001052-modified adipose-derived stem cells promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway[J].Stem Cell Res Ther,2022,13(1):336.DOI: 10.1186/s13287-022-03015-7.
[36]	ShiRF,JinYP,HuWW,et al.Exosomes derived from mmu_circ_0000250-modified adipose-derived mesenchymal stem cells promote wound healing in diabetic mice by inducing miR-128-3p/SIRT1-mediated autophagy[J].Am J Physiol Cell Physiol,2020,318(5):C848-C856.DOI: 10.1152/ajpcell.00041.2020.
[37]	LeeJ,LeeJH,ChakrabortyK,et al.Exosome-based drug delivery systems and their therapeutic applications[J].RSC Adv,2022,12(29):18475-18492.DOI: 10.1039/d2ra02351b.
[38]	LvQJ, DengJF, 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.
[39]	GondaliyaP, SayyedAA, BhatP, et al. Mesenchymal stem cell-derived exosomes loaded with miR-155 inhibitor ameliorate diabetic wound healing[J]. Mol Pharm,2022,19(5):1294-1308.DOI: 10.1021/acs.molpharmaceut.1c00669.
[40]	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.