-
摘要: 变应性鼻炎(allergic rhinitis，AR)是以上气道高反应为主要特征的鼻黏膜慢性炎症，涉及多种免疫细胞及炎性介质，目前以药物、免疫和手术治疗为主。研究发现，间充质干细胞具有免疫调节能力，在AR的治疗中具有临床应用前景。本文将从间充质干细胞的作用机制、其对AR关键细胞的免疫调节作用及目前应用面临的挑战展开综述，以期为AR的治疗提供新的思路。Abstract: Allergic rhinitis is a chronic nasal mucosal inflammation characterized by upper airway hyperresponsiveness, involving a variety of immune cells and inflammatory mediators. Drugs, immunotherapy, and surgical operation are the principal treatments at present. The study found that mesenchymal stem cells have the ability of immune regulation and have a promising clinical application in the treatment of allergic rhinitis. In this review, the action mechanism of mesenchymal stem cells, the immunomodulatory effect of mesenchymal stem cells on the key cells of allergic rhinitis, and the challenges of clinical application are reviewed, to provide new directions for the treatment of allergic rhinitis.
-
Key words:
- allergic rhinitis /
- mesenchymal stem cell /
- immune regulation
-
-
表 1 MSC对AR小鼠模型的治疗作用
MSC来源 动物模型 给药途径 给药剂量 治疗效果 参考文献 脂肪 Balb/c小鼠 静脉注射 2×107cells/mL，0.1 mL (+) [6] 脂肪 Balb/c小鼠 静脉注射 高浓度3×107cells/mL，0.1 mL低浓度1×107cells/mL，0.1 mL (+) [7] 脂肪 大鼠 腹腔注射 1×106cells/mL，0.5 mL (+) [8] 骨髓 Balb/c小鼠 静脉注射 0.5×106cells/mL，0.1 mL (+) [19] 骨髓 Balb/c小鼠 腹腔注射 细胞总量1×106cells2×106cells (+) [20] 骨髓 Balb/c小鼠 腹腔注射 含1×106cells上清 (+) [10] 脐带 Balb/c小鼠 腹腔注射 1×106cells/mL，0.1 mL (+) [12] 人脱落乳牙 Balb/c小鼠 腹腔注射 5×106cells/mL，0.1 mL (+) [16, 21] 鼻黏膜 小鼠 尾静脉注射 2×107cells/mL，0.1 mL (+) [15] 多能干细胞 Balb/c小鼠 腹腔注射 5×106cells/mL，0.1 mL (+) [18] 多能干细胞 Balb/c小鼠 静脉注射 1×108cells/kg，0.2 mL (+) [17] 
下载: 导出CSV
-
[1] 中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组, 中华医学会耳鼻咽喉头颈外科学分会鼻科学组. 中国变应性鼻炎诊断和治疗指南(2022年, 修订版)[J]. 中华耳鼻咽喉头颈外科杂志, 2022, 57(2): 106-129. doi: 10.3760/cma.j.cn115330-20211228-00828
[2] Zhao K, Lin R, Fan Z, et al. Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial[J]. J Hematol Oncol, 2022, 15(1): 22. doi: 10.1186/s13045-022-01240-4
[3] Lu J, Shen SM, Ling Q, et al. One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study[J]. Stem Cell Res Ther, 2021, 12(1): 340. doi: 10.1186/s13287-021-02417-3
[4] Petrou P, Kassis I, Levin N, et al. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis[J]. Brain, 2020, 143(12): 3574-3588. doi: 10.1093/brain/awaa333
[5] Vieujean S, Loly JP, Boutaffala L, et al. Mesenchymal stem cell injection in crohn's disease strictures: a phase Ⅰ-Ⅱ clinical study[J]. J Crohns Colitis, 2022, 16(3): 506-510. doi: 10.1093/ecco-jcc/jjab154
[6] Cho KS, Park HK, Park HY, et al. IFATS collection: Immunomodulatory effects of adipose tissue-derived stem cells in an allergic rhinitis mouse model[J]. Stem cells, 2009, 27(1): 259-265. doi: 10.1634/stemcells.2008-0283
[7] 李冠雪, 刘艳慧, 申聪香, 等. 脂肪来源间充质干细胞调控变应性鼻炎小鼠T细胞免疫状态的研究[J]. 中华耳鼻咽喉头颈外科杂志, 2016, 51(1): 50-56. doi: 10.3760/cma.j.issn.1673-0860.2016.01.008
[8] Ebrahim N, Mandour Y, Farid A, et al. Adipose tissue-derived mesenchymal stem cell modulates the immune response of allergic rhinitis in a rat model[J]. In J Mol Sci, 2019, 20(4): 873. doi: 10.3390/ijms20040873
[9] Zou B, Zhuang RX, Sun XY, et al. Analysis of the expression changes of IL-17+ gammadelta T cells and Treg cells in bone marrow mesenchymal stem cells targeted therapy for allergic rhinitis[J]. Eur Rev Med Pharmacol Sci, 2021, 25(7): 2858-2865.
[10] Zou W, Zou P, Zhang J, et al. Conditioned medium from the bone marrow mesenchymal stem cells modulates immune response via signal transduction and activator of transcription 6 signaling pathway in an allergic rhinitis mouse model[J]. Allergol Immunopathol(Madr), 2022, 50(4): 105-114. doi: 10.15586/aei.v50i4.572
[11] Fu Y, Kong Y, Li J, et al. Mesenchymal stem cells combined with traditional Chinese medicine(qi-fang-bi-min-tang) alleviates rodent allergic rhinitis[J]. J Cell Biochem, 2020, 121(2): 1541-1551. doi: 10.1002/jcb.29389
[12] Kan XL, Pan XH, Zhao J, et al. Effect and mechanism of human umbilical cord mesenchymal stem cells in treating allergic rhinitis in mice[J]. Sci Rep, 2020, 10(1): 19295. doi: 10.1038/s41598-020-76343-4
[13] Park IS, Kim DK, Kim JH, et al. Increased anti-allergic effects of secretome of low-level light treated tonsil-derived mesenchymal stem cells in allergic rhinitis Mouse Model[J]. Am J Rhinol Allergy, 2022, 36(2): 261-268. doi: 10.1177/19458924211053762
[14] Park I, Kim JH, Bae J, et al. The supernatant of tonsil-derived mesenchymal stem cell has antiallergic effects in allergic rhinitis mouse model[J]. Mediators Inflamm, 2020, 2020: 1-7.
[15] Yang C, Li J, Lin H, et al. Nasal mucosa derived-mesenchymal stem cells from mice reduce inflammation via modulating immune responses[J]. PLoS One, 2015, 10(3): e118849.
[16] Dai Y, Ni S, Ma K, et al. Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro[J]. Stem Cell Res. Ther, 2019, 10(1): 39. doi: 10.1186/s13287-019-1134-z
[17] Ma SY, Zhao N, Cui L, et al. Therapeutic effects of human pluripotent stem cell-derived mesenchymal stem cells on a murine model of acute type-2-dominated airway inflammation[J]. Stem Cell Rev Rep, 2022, 18(8): 2939-2951. doi: 10.1007/s12015-022-10389-x
[18] Zhong H, Fan XL, Fang SB, et al. Human pluripotent stem cell-derived mesenchymal stem cells prevent chronic allergic airway inflammation via TGF-beta1-Smad2/Smad3 signaling pathway in mice[J]. Mol Immunol, 2019, 109: 51-57. doi: 10.1016/j.molimm.2019.02.017
[19] Zhao N, Liu Y, Liang H, et al. Bone marrow-derived mesenchymal stem cells reduce immune reaction in a mouse model of allergic rhinitis[J]. Am J Transl Res, 2016, 8(12): 5628-5636.
[20] Işık S, Karaman M, Adan A, et al. Intraperitoneal mesenchymal stem cell administration ameliorates allergic rhinitis in the murine model[J]. Eur. Arch. Oto-Rhino-L, 2017, 274(1): 197-207. doi: 10.1007/s00405-016-4166-3
[21] Samivel R, Kim EH, Chung YJ, et al. Immunomodulatory effect of tonsil-derived mesenchymal stem cells in a mouse model of allergic rhinitis[J]. Am J Rhinol Allergy, 2015, 29(4): 262-267. doi: 10.2500/ajra.2015.29.4216
[22] Darlan DM, Munir D, Putra A, et al. MSCs-released TGFbeta1 generate CD4(+)CD25(+)Foxp3(+)in T-reg cells of human SLE PBMC[J]. J Formos Med Assoc, 2021, 120(1 Pt 3): 602-608.
[23] Guo Y, Peng Y, Zeng H, et al. Progress in mesenchymal stem cell therapy for ischemic stroke[J]. Stem Cells Int, 2021, 2021: 9923566.
[24] Lee HJ, Jung H, Kim DK. IDO and CD40 may be key molecules for immunomodulatory capacity of the primed tonsil-derived mesenchymal stem cells[J]. Int J Mol Sci, 2021, 22(11): 5772. doi: 10.3390/ijms22115772
[25] Marofi F, Alexandrovna KI, Margiana R, et al. MSCs and their exosomes: a rapidly evolving approach in the context of cutaneous wounds therapy[J]. Stem Cell Res Ther, 2021, 12(1): 597. doi: 10.1186/s13287-021-02662-6
[26] Yu X, Yu L, Guo B, et al. A narrative review of research advances in mesenchymal stem cell therapy for asthma[J]. Ann Transl Med, 2020, 8(21): 1461. doi: 10.21037/atm-20-6389
[27] 赵长青, 索利敏, 何韶衡, 等. 树突状细胞参与呼吸道过敏性疾病的研究进展[J]. 临床耳鼻咽喉头颈外科杂志, 2011, 25(12): 575-576. doi: 10.3969/j.issn.1001-1781.2011.12.018
[28] Lu Z, Meng S, Chang W, et al. Mesenchymal stem cells activate Notch signaling to induce regulatory dendritic cells in LPS-induced acute lung injury[J]. J Transl Med, 2020, 18(1): 241. doi: 10.1186/s12967-020-02410-z
[29] Peng YQ, Wu ZC, Xu ZB, et al. Mesenchymal stromal cells-derived small extracellular vesicles modulate DC function to suppress Th2 responses via IL-10 in patients with allergic rhinitis[J]. Eur J Immunol, 2022, 52(7): 1129-1140. doi: 10.1002/eji.202149497
[30] Scadding GK, Scadding GW. Innate and adaptive immunity: ILC2 and Th2 cells in upper and lower airway allergic diseases[J]. J Allergy Clin Immunol Pract, 2021, 9(5): 1851-1857. doi: 10.1016/j.jaip.2021.02.013
[31] Fu QL, Chow YY, Sun SJ, et al. Mesenchymal stem cells derived from human induced pluripotent stem cells modulate T-cell phenotypes in allergic rhinitis[J]. Allergy, 2012, 67(10): 1215-1222. doi: 10.1111/j.1398-9995.2012.02875.x.
[32] Fang SB, Zhang HY, Wang C, et al. Small extracellular vesicles derived from human mesenchymal stromal cells prevent group 2 innate lymphoid cell-dominant allergic airway inflammation through delivery of miR-146a-5p[J]. J Extracell Vesicles, 2020, 9(1): 1723260. doi: 10.1080/20013078.2020.1723260
[33] Zhao A, Yang Z, Sun R, et al. SerpinB2 is critical to Th2 immunity against enteric nematode infection[J]. J Immunol, 2013, 190(11): 5779-5787. doi: 10.4049/jimmunol.1200293
[34] Zhou J, Lu Y, Wu W, et al. HMSC-derived exosome inhibited Th2 cell differentiation via regulating miR-146a-5p/SERPINB2 pathway[J]. J Immunol Res, 2021, 2021: 1-11.
[35] Cahill EF, Tobin LM, Carty F, et al. Jagged-1 is required for the expansion of CD4+ CD25+ FoxP3+ regulatory T cells and tolerogenic dendritic cells by murine mesenchymal stromal cells[J]. Stem Cell Res Ther, 2015, 6(1): 19. doi: 10.1186/s13287-015-0021-5
[36] Zeng M, Chen Q, Ge S, et al. Overexpression of FoxM1 promotes differentiation of bone marrow mesenchymal stem cells into alveolar type Ⅱ cells through activating Wnt/beta-catenin signalling[J]. Biochem Biophys Res Commun, 2020, 528(2): 311-317. doi: 10.1016/j.bbrc.2020.05.042
[37] Kavuzlu A, Tatar EÇ, Karagöz T, et al. The effects of the stem cell on ciliary regeneration of injured rabbit sinonasal epithelium[J]. Eur Arch Oto-Rhino-L, 2017, 274(8): 3057-3064. doi: 10.1007/s00405-017-4595-7
[38] 严秀蕊, 陶金, 梁雪云. 人胎盘间充质干细胞来源外泌体保护氧化应激损伤肺上皮细胞的机制[J]. 中国组织工程研究, 2021, 25(19): 2994-2999. doi: 10.3969/j.issn.2095-4344.3537
[39] Duan HG, Ji F, Zheng CQ, et al. Human umbilical cord mesenchymal stem cells alleviate nasal mucosa radiation damage in a guinea pig model[J]. J Cell Biochem, 2015, 116(2): 331-338. doi: 10.1002/jcb.24975
[40] Cho BS, Kim JO, Ha DH, et al. Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis[J]. Stem Cell Res Ther, 2018, 9(1): 187. doi: 10.1186/s13287-018-0939-5
[41] Lin TY, Chang TM, Huang HC. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells attenuate mast cell activation[J]. Antioxidants(Basel), 2022, 11(11): 2279.
[42] Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions[J]. Blood, 2006, 107(1): 367-372. doi: 10.1182/blood-2005-07-2657
[43] Khare D, Or R, Resnick I, et al. Mesenchymal stromal cell-derived exosomes affect mRNA expression and function of B-lymphocytes[J]. Front Immunol, 2018, 9: 3053. doi: 10.3389/fimmu.2018.03053
[44] Fan X, Xu ZB, Li CL, et al. Mesenchymal stem cells regulate type 2 innate lymphoid cells via regulatory T cells through ICOS-ICOSL interaction[J]. Stem Cells, 2021, 39(7): 975-987. doi: 10.1002/stem.3369
[45] Lou H, Huang Y, Chen H, et al. M2 macrophages correlated with symptom severity and promote type 2 inflammation in allergic rhinitis[J]. Allergy, 2019, 74(11): 2255-2257. doi: 10.1111/all.13852
[46] Fang SB, Zhang HY, Meng XC, et al. Small extracellular vesicles derived from human MSCs prevent allergic airway inflammation via immunomodulation on pulmonary macrophages[J]. Cell Death Dis, 2020, 11(6): 409. doi: 10.1038/s41419-020-2606-x
[47] Panes J, Garcia-Olmo D, Van Assche G, et al. Long-term efficacy and safety of stem cell therapy(Cx601) for complex perianal fistulas in patients with crohn's disease[J]. Gastroenterology, 2018, 154(5): 1334-1342. doi: 10.1053/j.gastro.2017.12.020
[48] Cheng L, Wang S, Peng C, et al. Human umbilical cord mesenchymal stem cells for psoriasis: a phase 1/2a, single-arm study[J]. Signal Transduct Target Ther, 2022, 7(1): 263. doi: 10.1038/s41392-022-01059-y
[49] Campo A, Gonzalez-Ruiz JM, Andreu E, et al. Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis: a phase Ⅰ trial[J]. ERJ Open Res, 2021, 7(2): 00773-2020.
[50] Galipeau J, Sensebe L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities[J]. Cell Stem Cell, 2018, 22(6): 824-833. doi: 10.1016/j.stem.2018.05.004
-
计量
- 文章访问数: 270
- 施引文献: 0