表皮干细胞在皮肤创面修复中的作用与机制研究进展

石志远; 张博涵; 孙佳辰; 刘馨竹; 申传安

doi:10.3760/cma.j.cn501120-20211109-00382

表皮干细胞在皮肤创面修复中的作用与机制研究进展

doi: 10.3760/cma.j.cn501120-20211109-00382

解放军总医院第四医学中心烧伤整形医学部，北京　　100048

基金项目:

国家自然科学基金面上项目 82072169

军队后勤科研重大项目 ALB18J001

详细信息

通讯作者:
申传安，Email：shenchuanan@126.com

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出版历程
- 收稿日期: 2021-11-09

Research advances on the role and mechanism of epidermal stem cells in skin wound repair

Department of Burns and Plastic Surgery, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China

Funds:

General Program of National Natural Science Foundation of China 82072169

Major Program of Military Logistics Research Plan ALB18J001

More Information

Corresponding author: Shen Chuan'an, Email: shenchuanan@126.com

摘要

摘要: 表皮干细胞在皮肤自我更新、创面修复、再上皮化过程中发挥关键作用。单细胞测序、基因敲除等新技术新理念的出现进一步揭示了表皮干细胞维持表皮自我更新、参与创面修复的新机制，为创面修复提供了新思路。该文回顾了近年来关于表皮干细胞的增殖、分化、迁移的机制，通过对表皮干细胞异质性与可塑性相关研究的分析，进一步加深对表皮干细胞生理功能的理解；结合表皮干细胞在创面修复领域中的应用进展，为从事创面修复相关工作的临床与基础研究工作者提供参考。
- 皮肤 /
- 表皮干细胞 /
- 干细胞异质性 /
- 细胞可塑性 /
- 创面修复
Abstract: Epidermal stem cells play an pivotal role in skin self-renewal, wound repair, and re-epithelialization process. The emergence of new technologies and concepts such as single-cell sequencing and gene knockout further revealed a new mechanism of epidermal stem cells in epidermal self-renewal and wound repair, providing new ideas for wound repair. In this review, the mechanisms of proliferation, differentiation, and migration of epidermal stem cells are discussed. Combined with the analysis of researches on stem cell heterogeneity and cell plasticity, the physiological function of epidermal stem cells can be further understood. The application advances of epidermal stem cells in wound repair is also summarized, which would provide some advice for workers engaged in clinical and basic research on wound repair.
- Skin /
- Epidermal stem cells /
- Stem cell heterogeneity /
- Cell plasticity /
- Wound repair
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参考文献(44)

[1]	AlonsoL, FuchsE.Stem cells of the skin epithelium[J].Proc Natl Acad Sci U S A,2003,100(Suppl 1):S11830-11835.DOI: 10.1073/pnas.1734203100.
[2]	MuraiK, SkrupskelyteG, PiedrafitaG,et al.Epidermal tissue adapts to restrain progenitors carrying clonal p53 mutations[J].Cell Stem Cell,2018,23(5):687-699.e8.DOI: 10.1016/j.stem.2018.08.017.
[3]	PiedrafitaG, KostiouV, WabikA, et al. A single-progenitor model as the unifying paradigm of epidermal and esophageal epithelial maintenance in mice[J]. Nat Commun,2020,11(1):1429.DOI: 10.1038/s41467-020-15258-0.
[4]	Sánchez-DanésA, HannezoE, LarsimontJC, et al. Defining the clonal dynamics leading to mouse skin tumour initiation[J]. Nature,2016,536(7616):298-303.DOI: 10.1038/nature19069.
[5]	SadaA, JacobF, LeungE, et al. Defining the cellular lineage hierarchy in the interfollicular epidermis of adult skin[J]. Nat Cell Biol,2016,18(6):619-631.DOI: 10.1038/ncb3359.
[6]	MesaKR, KawaguchiK, CockburnK, et al. Homeostatic epidermal stem cell self-renewal is driven by local differentiation[J]. Cell Stem Cell,2018,23(5):677-686.e4.DOI: 10.1016/j.stem.2018.09.005.
[7]	ZouZR, LongX, ZhaoQ, et al.A single-cell transcriptomic atlas of human skin aging[J].Dev Cell,2021,56(3):383-397.e8.DOI: 10.1016/j.devcel.2020.11.002.
[8]	WangSX, DrummondML, Guerrero-JuarezCF, et al. Single cell transcriptomics of human epidermis identifies basal stem cell transition states[J]. Nat Commun,2020,11(1):4239.DOI: 10.1038/s41467-020-18075-7.
[9]	HeWY, YeJG, XuHY, et al. Differential expression of α6 and β1 integrins reveals epidermal heterogeneity at single-cell resolution[J]. J Cell Biochem,2020,121(3):2664-2676.DOI: 10.1002/jcb.29487.
[10]	HaenselD,JinSQ,SunP,et al.Defining epidermal basal cell states during skin homeostasis and wound healing using single-cell transcriptomics[J].Cell Rep,2020,30(11):3932-3947.e6.DOI: 10.1016/j.celrep.2020.02.091.
[11]	RadiceGP. The spreading of epithelial cells during wound closure in Xenopus larvae[J]. Dev Biol,1980,76(1):26-46.DOI: 10.1016/0012-1606(80)90360-7.
[12]	PaladiniRD, TakahashiK, BravoNS, et al. Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16[J]. J Cell Biol,1996,132(3):381-397.DOI: 10.1083/jcb.132.3.381.
[13]	AragonaM,DekoninckS,RulandsS,et al.Defining stem cell dynamics and migration during wound healing in mouse skin epidermis[J].Nat Commun,2017,8:14684.DOI: 10.1038/ncomms14684.
[14]	ParkS, GonzalezDG, GuiraoB, et al. Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice[J]. Nat Cell Biol,2017,19(2):155-163.DOI: 10.1038/ncb3472.
[15]	DonatiG, RognoniE, HiratsukaT, et al. Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of stem cell properties[J]. Nat Cell Biol,2017,19(6):603-613.DOI: 10.1038/ncb3532.
[16]	JoostS, JacobT, SunXY, et al. Single-cell transcriptomics of traced epidermal and hair follicle stem cells reveals rapid adaptations during wound healing[J]. Cell Rep,2018,25(3):585-597.e7.DOI: 10.1016/j.celrep.2018.09.059.
[17]	WierEM, GarzaLA. Through the lens of hair follicle neogenesis, a new focus on mechanisms of skin regeneration after wounding[J]. Semin Cell Dev Biol,2020,100:122-129.DOI: 10.1016/j.semcdb.2019.10.002.
[18]	GeYJ,GomezNC,AdamRC,et al.Stem cell lineage infidelity drives wound repair and cancer[J].Cell,2017,169(4):636-650.e14.DOI: 10.1016/j.cell.2017.03.042.
[19]	SubramaniamT,FauziMB,LokanathanY,et al.The role of calcium in wound healing[J].Int J Mol Sci,2021,22(12):6486.DOI: 10.3390/ijms22126486.
[20]	TuCL, CelliA, MauroT, et al. Calcium-sensing receptor regulates epidermal intracellular Ca2+ signaling and re-epithelialization after wounding[J]. J Invest Dermatol,2019,139(4):919-929.DOI: 10.1016/j.jid.2018.09.033.
[21]	OdaY, TuCL, MenendezA, et al. Vitamin D and calcium regulation of epidermal wound healing[J]. J Steroid Biochem Mol Biol,2016,164:379-385.DOI: 10.1016/j.jsbmb.2015.08.011.
[22]	Villarreal-PonceA, TirunehMW, LeeJ, et al. Keratinocyte-macrophage crosstalk by the Nrf2/Ccl2/EGF signaling axis orchestrates tissue repair[J]. Cell Rep,2020,33(8):108417.DOI: 10.1016/j.celrep.2020.108417.
[23]	HuangSM, WuCS, ChiuMH, et al. High glucose environment induces M1 macrophage polarization that impairs keratinocyte migration via TNF-α: an important mechanism to delay the diabetic wound healing[J]. J Dermatol Sci,2019,96(3):159-167.DOI: 10.1016/j.jdermsci.2019.11.004.
[24]	TurnerCT, WatersJM, JacksonJE, et al. Fibroblast-specific upregulation of Flightless I impairs wound healing[J]. Exp Dermatol,2015,24(9):692-697.DOI: 10.1111/exd.12751.
[25]	QiangL, YangS, CuiYH, et al. Keratinocyte autophagy enables the activation of keratinocytes and fibroblastsand facilitates wound healing[J]. Autophagy,2021,17(9):2128-2143.DOI: 10.1080/15548627.2020.1816342.
[26]	朱海杰,陈成,张小容,等. 树突状表皮T细胞调节小鼠表皮干细胞增殖和分化促进小鼠全层皮肤缺损创面愈合的机制研究[J].中华烧伤杂志,2020,36(10):905-914.DOI: 10.3760/cma.j.cn501120-20200623-00324.
[27]	4thHolmes JH, MolnarJA, ShuppJW, et al. Demonstration of the safety and effectiveness of the RECELL® System combined with split-thickness meshed autografts for the reduction of donor skin to treat mixed-depth burn injuries[J]. Burns,2019,45(4):772-782.DOI: 10.1016/j.burns.2018.11.002.
[28]	KowalS, KrugerE, BilirP, et al. Cost-effectiveness of the use of autologous cell harvesting device compared to standard of care for treatment of severe burns in the United States[J]. Adv Ther,2019,36(7):1715-1729.DOI: 10.1007/s12325-019-00961-2.
[29]	JohnstoneP, KweiJS, FilobbosG, et al. Successful application of keratinocyte suspension using autologous fibrin spray[J]. Burns,2017,43(3):e27-e30.DOI: 10.1016/j.burns.2016.05.010.
[30]	Klama-BaryłaA, KitalaD, ŁabuśW, et al. Autologous and allogeneic skin cell grafts in the treatment of severely burned patients: retrospective clinical study[J]. Transplant Proc,2018,50(7):2179-2187.DOI: 10.1016/j.transproceed.2017.11.079.
[31]	MalkocA, WongDT. Lessons learned from two survivors of greater than 90% total body surface area full thickness burn injuries using NovoSorb Biodegradable Temporizing MatrixTM and autologous skin cell suspension, RECELLTM: a case series[J]. J Burn Care Res,2021,42(3):577-585.DOI: 10.1093/jbcr/iraa176.
[32]	ShangYR, LiDW, ShenCA. The Benefit of microskin in combination with autologous keratinocyte suspension to treat full skin loss in vivo[J]. J Burn Care Res,2017,38(6):348-353.DOI: 10.1097/BCR.0000000000000552.
[33]	LuGZ, CaiLL, ZhaoP, et al. Mixed suspension of cultured autologous and allogenic keratinocytes in fibrin glue for the treatment of full-thickness burns[J]. Wounds,2011,23(2):32-37.
[34]	YoonJ, YangHT, YimH, et al. Effectiveness and safety of a thermosensitive hydrogel cultured epidermal allograft for burns[J]. Adv Skin Wound Care,2017,30(12):559-564.DOI: 10.1097/01.ASW.0000526882.14740.01.
[35]	CheshireP, ZhafiraAS, BanakhI, et al. Xeno-free expansion of adult keratinocytes for clinical application: the use of human-derived feeder cells and serum[J]. Cell Tissue Res,2019,376(3):389-400.DOI: 10.1007/s00441-018-02986-5.
[36]	HassanzadehH, MatinMM, Naderi-MeshkinH, et al. Using paracrine effects of Ad-MSCs on keratinocyte cultivation and fabrication of epidermal sheets for improving clinical applications[J]. Cell Tissue Bank,2018,19(4):531-547.DOI: 10.1007/s10561-018-9702-5.
[37]	姜耀男,王雨翔,郑勇军,等.含异体角质形成细胞和成纤维细胞的细胞膜片治疗Ⅱ度烧伤创面的临床研究[J].中华烧伤杂志,2020,36(3):171-178. DOI: 10.3760/cma.j.cn501120-20191113-00426.
[38]	JacksonCJ, ReppeS, EidetJR, et al. Optimization of storage temperature for retention of undifferentiated cell character of cultured human epidermal cell sheets[J]. Sci Rep,2017,7(1):8206.DOI: 10.1038/s41598-017-08586-7.
[39]	RingstadH, ReppeS, SchøyenTH,et al.Stem cell function is conserved during short-term storage of cultured epidermal cell sheets at 12 ℃[J].PLoS One,2020,15(5):e0232270.DOI: 10.1371/journal.pone.0232270.
[40]	MotamediS, EsfandpourA, BabajaniA,et al.The current challenges on spray-based cell delivery to the skin wounds[J].Tissue Eng Part C Methods,2021,27(10):543-558.DOI: 10.1089/ten.TEC.2021.0158.
[41]	Esteban-VivesR, CorcosA, ChoiMS, et al. Cell-spray auto-grafting technology for deep partial-thickness burns: problems and solutions during clinical implementation[J]. Burns,2018,44(3):549-559.DOI: 10.1016/j.burns.2017.10.008.
[42]	MolnarJA, WalkerN, SteeleTN, et al. Initial experience with autologous skin cell suspension for treatment of deep partial-thickness facial burns[J]. J Burn Care Res,2020,41(5):1045-1051.DOI: 10.1093/jbcr/iraa037.
[43]	Esteban-VivesR, YoungM, OverP, et al. In vitro keratinocyte expansion for cell transplantation therapy is associated with differentiation and loss of basal layer derived progenitor population[J]. Differentiation,2015,89(5):137-145. DOI: 10.1016/j.diff.2015.05.002.
[44]	ChemaliM, LaurentA, ScalettaC, et al. Burn center organization and cellular therapy integration: managing risks and costs[J]. J Burn Care Res,2021,42(5):911-924.DOI: 10.1093/jbcr/irab080.