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中华妇幼临床医学杂志(电子版) ›› 2019, Vol. 15 ›› Issue (05) : 492 -496. doi: 10.3877/cma.j.issn.1673-5250.2019.05.003

所属专题: 文献

专家约稿

间充质干细胞通过调控巨噬细胞极化实现免疫应答的研究现状
何萌1, 陈娟1, 伍金林1,()   
  1. 1. 四川大学华西第二医院儿科、出生缺陷与相关妇儿疾病教育部重点实验室,成都 610041
  • 收稿日期:2019-04-29 修回日期:2019-08-02 出版日期:2019-10-01
  • 通信作者: 伍金林

Current status of immune response of mesenchymal stem cells by regulating the polarization of macrophages

Meng He1, Juan Chen1, Jinlin Wu1,()   

  1. 1. Department of Pediatrics, Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2019-04-29 Revised:2019-08-02 Published:2019-10-01
  • Corresponding author: Jinlin Wu
  • About author:
    Corresponding author: Wu Jinlin, Email:
  • Supported by:
    Key Project of Health and Family Planning Commission of Sichuan Province(16ZD019)
引用本文:

何萌, 陈娟, 伍金林. 间充质干细胞通过调控巨噬细胞极化实现免疫应答的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2019, 15(05): 492-496.

Meng He, Juan Chen, Jinlin Wu. Current status of immune response of mesenchymal stem cells by regulating the polarization of macrophages[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2019, 15(05): 492-496.

间充质干细胞(MSC)是一种具有自我更新及多向分化潜能的多能干细胞,是细胞移植治疗的研究热点。既往认为,MSC主要通过细胞替代达到治疗疾病的目的。近年多项研究结果表明,MSC在调控免疫应答、抑制炎症反应中,也具有重要作用。新生儿缺血缺氧性脑病(HIE)是引起新生儿死亡和伤残的重要原因。对HIE采取MSC移植治疗,可减轻缺血缺氧引起的炎症损伤,加速神经修复。然而,MSC的免疫调控作用并不是与生俱来的,而与局部炎症微环境密切相关,在不同水平炎症因子的刺激下,MSC可表现出截然不同的免疫作用。深入探讨MSC的免疫调控机制,有助于进一步对其临床应用进行研究。笔者拟就炎症微环境刺激下,MSC的免疫调控作用及其机制进行阐述。

Mesenchymal stem cells (MSC) are stem cells with abilities of self-renewal and multidirectional differentiation. In the past, MSC have been considered to achieve therapeutic effects mainly through cell replacement. However, a number of studies have shown that MSC play an important role in regulating immune response and inhibiting inflammatory response. Hypoxic ischemic encephalopathy (HIE) of neonates is an important disease that causes death and disability of neonates. Studies have proved that MSC transplantation can reduce inflammatory injury caused by ischemia and hypoxia, and accelerate nerve repair. However, the immunomodulatory effect of MSC is not innate, but closely related to the local inflammatory microenvironment. Under the stimulation of different levels of inflammatory factors, MSC may show distinct immune effects. In-depth understanding of its immune regulation mechanism is conducive to further research on its clinical application. Therefore, this article elaborates the immune regulation effect and mechanism of MSC under the stimulation of inflammatory microenvironment.

[1]
Castro-Manrreza ME, Montesinos JJ. Immunoregulation by mesenchymal stem cells: biological aspects and clinical applications[J]. J Immunol Res, 2015, 2015: 394917.
[2]
Ball LM, Bernardo ME, Roelofs H, et al. Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid-refractory, grade Ⅲ-Ⅳ acute graft-versus-host disease[J]. Br J Haematol, 2013, 163(4): 501-509.
[3]
Archambault J, Moreira A, McDaniel D, et al. Therapeutic potential of mesenchymal stromal cells for hypoxic ischemic encephalopathy: a systematic review and Meta-analysis of preclinical studies[J]. PLoS One, 2017, 12(12): e0189895.
[4]
Li W, Zhang Q, Wang M, et al. Macrophages are involved in the protective role of human umbilical cord-derived stromal cells in renal ischemia-reperfusion injury[J]. Stem Cell Res, 2013, 10(3): 405-416.
[5]
Ben-Mordechai T, Holbova R, Landa-Rouben N, et al.Macrophage subpopulations are essential for infarct repair with and without stem cell therapy[J]. J Am Coll Cardiol, 2013, 62(20): 1890-1901.
[6]
Panés J, García-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn′s disease: a phase 3 randomised, double-blind controlled trial[J]. Lancet, 2016, 388(10051): 1281-1290.
[7]
Rocha-Ferreira E, Hristova M. Antimicrobial peptides and complement in neonatal hypoxia-ischemia induced brain damage[J]. Front Immunol, 2015, 6(1): 56.
[8]
Jacobs SE, Morley CJ, Inder TE, et al. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial[J]. Arch Pediatr Adolesc Med, 2011, 165(8): 692-700.
[9]
Schwerk A, Altschüler J, Roch M, et al. Human adipose-derived mesenchymal stromal cells increase endogenous neurogenesis in the rat subventricular zone acutely after 6-hydroxydopamine lesioning[J]. Cytotherapy, 2015, 17(2): 199-214.
[10]
Salehi H, Amirpour N, Niapour A, et al. An overview of neural differentiation potential of human adipose derived stem cells[J]. Stem Cell Rev, 2016, 12(1): 26-41.
[11]
Ma S, Xie N, Li W, et al. Immunobiology of mesenchymal stem cells[J]. Cell Death Differ, 2014, 21(2): 216-225.
[12]
Peng Y, Chen X, Liu Q, et al. Mesenchymal stromal cells infusions improve refractory chronic graft versus host disease through an increase of CD5 regulatory B cells producing interleukin 10[J]. Leukemia, 2015, 29(3): 636-646.
[13]
Fu ZW, Zhang ZY, Ge HY. Mesenteric injection of adipose-derived mesenchymal stem cells relieves experimentally-induced colitis in rats by regulating Th17/Treg cell balance[J]. Am J Transl Res, 2018, 10(1): 54-66.
[14]
Wang Q, Qian S, Li J, et al. Combined transplantation of autologous hematopoietic stem cells and allogenic mesenchymal stem cells increases T regulatory cells in systemic lupus erythematosus with refractory lupus nephritis and leukopenia[J]. Lupus, 2015, 24(11): 1221-1226.
[15]
Baharlou R, Ahmadi-Vasmehjani A, Faraji F, et al. Human adipose tissue-derived mesenchymal stem cells in rheumatoid arthritis: Regulatory effects on peripheral blood mononuclear cells activation[J]. Int Immunopharmacol, 2017, 47(1): 59-69.
[16]
Wang Y, Chen XD, Cao W, et al. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications[J]. Nat Immunol, 2014, 15(11): 1009-1016.
[17]
Sudres M, Norol F, Trenado A, et al. Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice[J]. J Immunol, 2006, 176(12): 7761-7767.
[18]
Polchert D, Sobinsky J, Douglas G, et al. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease[J]. Eur J Immunol, 2008, 38(6): 1745-1755.
[19]
Waterman RS, Tomchuck SL, Henkle SL, et al. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype[J]. PLoS One, 2010, 5(4): e10088.
[20]
Brandau S, Jakob M, Hemeda H, et al. Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge[J]. J Leukoc Biol, 2010, 88(5): 1005-1015.
[21]
Chatterjee D, Marquardt N, Tufa DM, et al. Human umbilical cord-derived mesenchymal stem cells utilize activin-A to suppress interferon-γ production by natural killer cells[J]. Front Immunol, 2014, 5: 662.
[22]
Spaggiari GM, Capobianco A, Becchetti S, et al. Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation[J]. Blood, 2006, 107(4): 1484-1490.
[23]
Domenis R, Cifù A, Quaglia S, et al. Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes[J]. Sci Rep, 2018, 8(1): 13325.
[24]
Murry PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines[J]. Immunity, 2014, 41(1): 14-20.
[25]
Abumaree MH, Jumah MA, Kalionis B, et al. Human placental mesenchymal stem cells (pMSCs) play a role as immune suppressive cells by shifting macrophage differentiation from inflammatory M1 to anti-inflammatory M2 macrophages[J]. Stem Cell Rev Report, 2013, 9(5): 620-641.
[26]
Freytes DO, Kang JW, Marcos-Campos I, et al. Macrophages modulate the viability and growth of human mesenchymal stem cells[J]. J Cell Biochem, 2013, 114(1): 220-229.
[27]
Cho DI, Kim MR, Jeong HY, et al. Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages[J]. Exp Mol Med, 2014, 46(1): e70.
[28]
Park HJ, Kim J, Saima FT, et al. Adipose-derived stem cells ameliorate colitis by suppression of inflammasome formation and regulation of M1-macrophage population through prostaglandin E2[J]. Biochem Biophys Res Commun, 2018, 498(4): 988-995.
[29]
Holladay CA, Duffy AM, Chen X, et al. Recovery of cardiac function mediated by MSC and interleukin-10 plasmid functionalised scaffold[J]. Biomaterials, 2012, 33(5): 1303-1314.
[30]
Donega V, Nijboer CH, van Tilborg G, et al. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury[J]. Exp Neurol, 2014, 261(1): 53-64.
[31]
Jung M, Ma Y, Iyer RP, et al. IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation[J]. Basic Res Cardiol, 2017, 112(3): 33.
[32]
Németh K, Leelahavanichkul A, Yuen PST, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production[J]. Nat Med, 2009, 15(1): 42-49.
[33]
Ylöstalo JH, Bartosh TJ, Coble K, et al. Human mesenchymal stem/stromal cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype[J]. Stem Cells, 2012, 30(10): 2283-2296.
[34]
Yasui M, Tamura Y, Minami M, et al. The prostaglandin E2 receptor EP4 regulates obesity-related inflammation and insulin sensitivity[J]. PLoS One, 2015, 10(8): e0136304.
[35]
Lee S, Zhang QZ, Karabucak B, et al. DPSCs from inflamed pulp modulate macrophage function via the TNF-α/IDO axis[J]. J Dent Res, 2016, 95(11): 1274-1281.
[36]
François M, Romieu-Mourez R, Li M, et al. Human MSC suppression correlates with cytokine induction of indoleamine 2, 3-dioxygenase and bystander M2 macrophage differentiation[J]. Mol Ther, 2012, 20(1): 187-195.
[37]
Corrado C, Raimondo S, Chiesi A, et al. Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications[J]. Int J Mol Sci, 2013, 14(3): 5338-5366.
[38]
Ti DD, Hao HJ, Tong C, 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(1): 308.
[39]
Melief SM, Schrama E, Brugman MH, et al. Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages[J]. Stem Cell, 2013, 31(9): 1980-1991.
[40]
Konala VB, Mamidi MK, Bhonde R, et al. The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration[J]. Cytotherapy, 2016, 18(1): 13-24.
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