干细胞在汗腺再生中的应用研究进展

张静娟; 王茂英; 赵洁; 姜笃银

doi:10.3760/cma.j.cn501120-20210123-00033

干细胞在汗腺再生中的应用研究进展

doi: 10.3760/cma.j.cn501120-20210123-00033

1.
山东大学齐鲁医学院第二临床学院，济南　　250012
2.
山东大学第二医院急诊医学　中心，济南　　250033

基金项目:

国家自然科学基金面上项目 81372074, 81873934

山东省科技攻关项目 2015GSF118041

济南市科技发展计划 201704129

王正国创伤医学发展基金会生长因子复兴计划 SZYZ-TR-09

详细信息

通讯作者:
姜笃银，Email：jdybs2@vip.163.com

计量
- 文章访问数: 253
- HTML全文浏览量: 94
- PDF下载量: 31
- 被引次数: 0
出版历程
- 收稿日期: 2021-01-23

Research advances on the application of stem cells in sweat gland regeneration

1.
The Second Clinical College, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
2.
Department of Emergency, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China

Funds:

General Program of National Natural Science Foundation of China 81372074, 81873934

Key Science and Technology Projects of Shandong Province of China 2015GSF118041

Science and Technology Development Projects of Jinan 201704129

Wang Zhengguo Foundation for Traumatic Medicine Growth Factor Rejuvenation Plan SZYZ-TR-09

More Information

Corresponding author: Jiang Duyin, Email: jdybs2@vip.163.com

摘要

摘要:
汗腺作为皮肤的重要附属器官之一，对体温调节和内环境稳态维持起重要作用。烧伤后汗腺遭到破坏，无法进行自我修复，最终遗留排汗障碍问题，而目前的临床治疗策略均无法有效恢复损伤汗腺的功能。因此亟待寻求能够促进汗腺再生并恢复其正常功能的治疗手段。干细胞来源广泛、免疫原性低、增殖能力强且具有多向分化潜能等优势，已成为再生医学领域的研究热点。近年来已有多种干细胞被诱导分化为具有一定分泌功能的汗腺样组织，为临床烧伤后汗腺再生提供了治疗方向。本文主要从不同环境中干细胞转化为汗腺细胞的方式及其影响因素方面，就干细胞在汗腺再生中的应用研究进展进行综述。
- 烧伤 /
- 干细胞 /
- 汗腺 /
- 伤口愈合
Abstract:
Sweat gland is one of the important appendage organs of the skin, which plays an important role in thermoregulation and homeostasis maintenance. Sweat glands are damaged and unable to self-repair after burns, resulting in perspiration disorders eventually. However, current clinical strategies cannot restore the function of the damaged sweat glands effectively. Therefore, it is urgent to seek treatments that can promote the regeneration of sweat glands and restore their normal functions. Stem cells have extensive sources, low immunogenicity, high proliferation capacity, and multi-directional differentiation potential, which have become a focus in the field of regenerative medicine. In recent years, a variety of stem cells have been induced to differentiate into sweat gland-like tissue with certain secretory function, which provides treatment direction for sweat gland regeneration after burns in clinic. This article reviews the recent research advances on the application of stem cells in sweat gland regeneration from the perspectives of the manner by which stem cells transform into sweat gland cells in different environments and their influencing factors.
- Burns /
- Stem cells /
- Sweat glands /
- Wound healing
所有作者均声明不存在利益冲突

脓毒症作为一种严重感染诱发的临床综合征，其导致的病死率居高不下。腹腔感染作为ICU中第2常见的感染病因，往往会导致并发症的发生率和病死率增加。解放军总医院医学创新研究部转化医学研究中心姚咏明教授团队近期在《Burns & Trauma》发文《Predictive value of immune cell counts and neutrophil-to-lymphocyte ratio for 28-day mortality in patients with sepsis caused by intra-abdominal infection》，该研究选取216例符合脓毒症3.0诊断标准及纳入标准的患者作为研究对象。该研究对患者入院后第1、3、5、7天外周血中性粒细胞、淋巴细胞、单核细胞数量和中性粒细胞/淋巴细胞比值（NLR）进行广义线性模型分析，结果显示死亡组患者单核细胞和淋巴细胞数量均比存活组低（第1天的单核细胞除外）。存活组患者免疫细胞数量呈时间依赖性升高趋势，而死亡组患者免疫细胞数量在短暂升高之后出现明显下降。该研究进一步通过构建单因素及多因素Cox回归模型分析显示，患者入院第3天的单核细胞数量、第5天的淋巴细胞数量以及第7天的单核细胞、淋巴细胞数量及NLR是腹腔感染导致脓毒症患者28 d内死亡的独立预测因子。该研究以独特的视角揭示了脓毒症患者免疫状态改变的临床意义和应用价值。

刘双庆，编译自《Burns Trauma》,2021,9:tkaa040；姚咏明，审校

HTML全文

参考文献(37)

[1]	刘煜凡,黄沙,付小兵.皮肤附属器汗腺发育及功能的机制研究[J].生命科学,2020,32(3):219-226.DOI: 10.13376/j.cbls/2020030.
[2]	ChenR,ZhuZ,JiS,et al.Sweat gland regeneration: current strategies and future opportunities[J].Biomaterials,2020,255:120201.DOI: 10.1016/j.biomaterials.2020.120201.
[3]	姜笃银,宗宪磊,付小兵,等.深Ⅱ度烧伤创面汗腺干细胞标志物的变化规律[J].中华烧伤杂志,2009,25(4):301-304.DOI: 10.3760/cma.j.issn.1009-2587.2009.04.025.
[4]	WangX,WangX,LiuJ,et al.Hair follicle and sebaceous gland de novo regeneration with cultured epidermal stem cells and skin-derived precursors[J].Stem Cells Transl Med,2016,5(12):1695-1706.DOI: 10.5966/sctm.2015-0397.
[5]	LinMJ,LuCP.Glandular stem cells in the skin during development, homeostasis, wound repair and regeneration[J].Exp Dermatol,2021,30(4):598-604.DOI: 10.1111/exd.14319.
[6]	BrandenburgerM,KruseC.Heterogeneity of sweat gland stem cells[J].Adv Exp Med Biol,2019,1169:55-62.DOI: 10.1007/978-3-030-24108-7_3.
[7]	MaY,LiM,LiuJ,et al.Location, isolation, and identification of mesenchymal stem cells from adult human sweat glands[J].Stem Cells Int,2018,2018:2090276.DOI: 10.1155/2018/2090276.
[8]	LiaoT,LehmannJ,SternsteinS,et al.Nestin+ progenitor cells isolated from adult human sweat gland stroma promote reepithelialisation and may stimulate angiogenesis in wounded human skin ex vivo[J].Arch Dermatol Res,2019,311(4):325-330.DOI: 10.1007/s00403-019-01889-x.
[9]	FuX,LiJ,SunX,et al.Epidermal stem cells are the source of sweat glands in human fetal skin: evidence of synergetic development of stem cells, sweat glands, growth factors, and matrix metalloproteinases[J].Wound Repair Regen,2005,13(1):102-108.DOI: 10.1111/j.1067-1927.2005.130113.x.
[10]	LiJ,FuX,SunX,et al.The interaction between epidermal growth factor and matrix metalloproteinases induces the development of sweat glands in human fetal skin[J].J Surg Res,2002,106(2):258-263.DOI: 10.1006/jsre.2002.6469.
[11]	LiH,FuX,OuyangY,et al.Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages[J].Cell Tissue Res,2006,326(3):725-736.DOI: 10.1007/s00441-006-0270-9.
[12]	李海红,付小兵,欧阳云淑,等.人骨髓间充质干细胞表型转化为汗腺细胞的体外研究[J].中华创伤杂志,2006,22(2):81-86.DOI: 10.3760/j:issn:1001-8050.2006.02.001.
[13]	陈艳,赵洪良,谭志军,等.人骨髓间充质干细胞向汗腺样细胞诱导分化的研究[J].感染、炎症、修复,2014,15(2):76-78.DOI: 10.3969/j.issn.1672-8521.2014.02.003.
[14]	XuY,HongY,XuM,et al.Role of keratinocyte growth factor in the differentiation of sweat gland-like cells from human umbilical cord-derived mesenchymal stem cells[J].Stem Cells Transl Med,2016,5(1):106-116.DOI: 10.5966/sctm.2015-0081.
[15]	TaoR,SunTJ,HanYQ,et al.Epimorphin-induced differentiation of human umbilical cord mesenchymal stem cells into sweat gland cells[J].Eur Rev Med Pharmacol Sci,2014,18(9):1404-1410.
[16]	HuT,XuY,YaoB,et al.Developing a novel and convenient model for investigating sweat gland morphogenesis from epidermal stem cells[J].Stem Cells Int,2019,2019:4254759.DOI: 10.1155/2019/4254759.
[17]	LiangH,SunQ,ZhenY,et al.The differentiation of amniotic fluid stem cells into sweat glandlike cells is enhanced by the presence of Sonic hedgehog in the conditioned medium[J].Exp Dermatol,2016,25(9):714-720.DOI: 10.1111/exd.13062.
[18]	WangY,LiuZY,ZhaoQ,et al.Future application of hair follicle stem cells: capable in differentiation into sweat gland cells[J]. Chin Med J(Engl),2013,126(18):3545-3552.DOI: 10.3760/cma.j.issn.0366-6999.20130931.
[19]	FukutakeM,OchiaiD,MasudaH,et al.Human amniotic fluid stem cells have a unique potential to accelerate cutaneous wound healing with reduced fibrotic scarring like a fetus[J].Hum Cell,2019,32(1):51-63.DOI: 10.1007/s13577-018-0222-1.
[20]	CaiS,PanY,HanB,et al. Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands[J].Chin Med J(Engl),2011,124(15):2260-2268.DOI: 10.3760/cma.j.issn.0366-6999.2011.15.004.
[21]	SunS,XiaoJ,HuoJ,et al.Targeting ectodysplasin promotor by CRISPR/dCas9-effector effectively induces the reprogramming of human bone marrow-derived mesenchymal stem cells into sweat gland-like cells[J].Stem Cell Res Ther,2018,9(1):8.DOI: 10.1186/s13287-017-0758-0.
[22]	ChenY,LiQ,TanZ,et al.MicroRNA-mediated regulation of BM-MSCs differentiation into sweat gland-like cells: targeting NF-κB[J].J Mol Histol,2019,50(2):155-166.DOI: 10.1007/s10735-019-09814-2.
[23]	宋志芳,刘德伍,彭燕,等.miRNA-203转染诱导人表皮干细胞向汗腺细胞分化的研究[J].中国修复重建外科杂志,2015,29(3):343-350.DOI: 10.7507/1002-1892.20150073.
[24]	WangY,WangR,YaoB,et al.TNF-α suppresses sweat gland differentiation of MSCs by reducing FTO-mediated m6 A-demethylation of Nanog mRNA[J].Sci China Life Sci,2020,63(1):80-91.DOI: 10.1007/s11427-019-9826-7.
[25]	HuS,YuanJ,XuJ,et al.TNF-α and IFN-γ synergistically inhibit the repairing ability of mesenchymal stem cells on mice colitis and colon cancer[J].Am J Transl Res,2019,11(9):6207-6220.
[26]	赵换军,丁路,付潇潇,等.HDAC4基因甲基化对hMSCs向汗腺样细胞诱导转分化的影响[J].中国应用生理学杂志,2018,34(4):360-363.DOI: 10.12047/j.cjap.5584.2018.082.
[27]	陈甫寰,宋慧锋,郭希民,等.氧还蛋白过氧化物2在表皮干细胞向汗腺细胞诱导分化过程中对表型改变的影响[J].中华整形外科杂志,2017,33(1):37-42.DOI: 10.3760/cma.j.issn.1009-4598.2017.01.010.
[28]	YaoB,SongW,LiZ,et al.Irf6 directs glandular lineage differentiation of epidermal progenitors and promotes limited sweat gland regeneration in a mouse burn model[J].Stem Cell Res Ther,2018,9(1):179.DOI: 10.1186/s13287-018-0929-7.
[29]	刘坤坤,赵亚平,高玮,等.体外构建干细胞汗腺细胞融合体的初步研究[J].河北医药,2019,41(20):3130-3133.DOI: 10.3969/j.issn.1002-7386.2019.20.020.
[30]	ZhangM,LiH,ChenL,et al.Three-dimensional reconstructed eccrine sweat glands with vascularization and cholinergic and adrenergic innervation[J].J Mol Histol,2018,49(4):339-345.DOI: 10.1007/s10735-018-9773-4.
[31]	YaoB,WangR,WangY,et al.Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration[J].Sci Adv,2020,6(10):eaaz1094.DOI: 10.1126/sciadv.aaz1094.
[32]	王睿生物3D打印的微环境诱导乳腺祖细胞向汗腺细胞分化的研究天津天津医科大学2019DOI:10.27366/d.cnki.gtyku.2019.000990 王睿.生物3D打印的微环境诱导乳腺祖细胞向汗腺细胞分化的研究[D].天津:天津医科大学,2019.DOI:10.27366/d.cnki.gtyku.2019.000990.
[33]	LiuY,LiZ,LiJ,et al.Stiffness-mediated mesenchymal stem cell fate decision in 3D-bioprinted hydrogels[J/OL].Burns Trauma,2020,8:tkaa029[2021-01-23]. https://academic.oup.com/burnstrauma/article/doi/ 10.1093/burnst/tkaa029/5876593.DOI: 10.1093/burnst/tkaa029.
[34]	LiuY,LiJ,YaoB,et al.The stiffness of hydrogel-based bioink impacts mesenchymal stem cells differentiation toward sweat glands in 3D-bioprinted matrix[J].Mater Sci Eng C Mater Biol Appl,2021,118:111387.DOI: 10.1016/j.msec.2020.111387.
[35]	陈润开,付小兵,孙晓艳.体外构建工程化汗腺类器官的初步研究[J].解放军医学杂志,2020,45(4):384-390.DOI: 10.11855/j.issn.0577-7402.2020.04.07.
[36]	LeiM,SchumacherLJ,LaiYC,et al.Self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells[J].Proc Natl Acad Sci U S A,2017,114(34):E7101-E7110.DOI: 10.1073/pnas.1700475114.
[37]	DiaoJ,LiuJ,WangS,et al.Sweat gland organoids contribute to cutaneous wound healing and sweat gland regeneration[J].Cell Death Dis,2019,10(3):238.DOI: 10.1038/s41419-019-1485-5.