间充质干细胞来源的细胞外囊泡:免疫相关疾病的理想细胞替代疗法
摘要
间充质干细胞(mesenchymal stem cell, MSC)作为一种具有多向分化潜能的非造血干细胞,已被应用于多种组织损伤与免疫相关疾病的治疗。MSC获得如此广泛应用的原因与其强大的促进受损组织再生和免疫调控功能密不可分。近年来,MSC的免疫调控功能已在多种免疫相关疾病的治疗中得到广泛验证。研究表明,MSC免疫调节作用的发挥主要通过旁分泌,其中,MSC分泌的细胞外囊泡(extracellular vesicle, EV)发挥着重要作用。EV可以复制MSC的多种免疫调节功能,但是,MSC-EV在MSC的免疫调节中具体发挥哪些作用,MSC-EV能否替代MSC用于免疫相关疾病的治疗?文章结合以上问题,对近年来MSC与MSC-EV的免疫调控功能进行综述。
引文
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[3] Dotoli GM, De Santis GC, Orellana MD, et al. Mesenchymal stromal cell infusion to treat steroid-refractory acute GvHD Ⅲ/Ⅳ after hematopoietic stem cell transplantation[J]. Bone Marrow Transplant, 2017, 52(6): 859-862.
[4] Fiorina P, Jurewicz M, Augello A, et al. Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes[J]. J Immunol, 2009, 183(2): 993-1004.
[5] Sharma J, Hampton JM, Valiente GR, et al. Therapeutic development of mesenchymal stem cells or their extracellular vesicles to inhibit autoimmune-mediated inflammatory proce-sses in systemic lupus erythematosus[J]. Front Immunol, 2017, 8: 526.
[6] Tanaka Y. Human mesenchymal stem cells as a tool for joint repair in rheumatoid arthritis[J]. Clin Exp Rheumatol, 2015, 33(4 Suppl 92): S58-S62.
[7] Zhang XM, Zhang YJ, Wang W, et al. Mesenchymal stem cells to treat Crohn's disease with fistula[J]. Hum Gene Ther, 2017, 28(7): 534-540.
[8] Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function[J]. Stem Cell Res Ther, 2016, 7(1): 125.
[9] Wang D, Niu L, Feng X, et al. Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: A 6-year follow-up study[J]. Clin Exp Med, 2017, 17(3): 333-340.
[10] Giebel B, Kordelas L, B?rger V.Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles[J]. Stem Cell Investig, 2017, 4: 84.
[11] Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses[J]. Blood, 2005, 105(4): 1815-1822.
[12] Sivanathan KN, Rojas-Canales DM, Hope CM, et al. Interleukin-17A-induced human mesenchymal stem cells are superior modulators of immunological function[J]. Stem Cell, 2015, 33(9): 2850-2863.
[13] Akiyama K, Chen C, Wang D, et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis[J]. Cell Stem Cell, 2012, 10(5): 544-555.
[14] Ben-Ami E, Berrih-Aknin S, Miller A.Mesenchymal stem cells as an immunomodulatory therapeutic strategy for autoimmune diseases[J]. Autoimmun Rev, 2011,10(7): 410-415.
[15] Wang SS, Jia J, Wang Z. Mesenchymal stem cell-derived extracellular vesicles suppresses iNOS expression and ameliorates neural impairment in Alzheimer's disease mice[J]. J Alzheimers Dis, 2018, 61(3): 1005-1013.
[16] Cho KA, Lee JK, Kim YH, et al. Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner[J]. Cell Mol Immunol, 2017.
[17] Wang W, Li H, Xu F, et al. IFN-γ up-regulates PD-L1 expression in human placenta mesenchymal stem cells and enhances cell ability to induce the differentiation of IL-10+ T cells from cord blood- and peripheral blood-derived T cells[J]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2016, 32(2): 191-195.
[18] Lo Sicco C, Reverberi D, Balbi C, et al. Mesenchymal stem cell-derived extracellular vesicles as mediators of anti-inflammatory effects: Endorsement of macrophage polarization[J]. Stem Cell Transl Med, 2017, 6(3): 1018-1028.
[19] Henao Agudelo JS, Braga TT, Amano MT, et al. Mesenchymal stromal cell-derived microvesicles regulate an internal pro-inflammatory program in activated macrophages[J]. Front Immunol, 2017, 8: 881.
[20] Jiang XX, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells[J]. Blood, 2005, 105(10): 4120-4126.
[21] Tkach M, Théry C.Communication by extracellular vesicles: Where we are and where we need to go[J]. Cell, 2016, 164(6): 1226-1232.
[22] Sun Y, Kong W, Huang S, et al. Comparable therapeutic potential of umbilical cord mesenchymal stem cells in collagen-induced arthritis to TNF inhibitor or anti-CD20 treatment[J]. Clin Exp Rheumatol, 2017, 35(2): 288-295.
[23] Monguió-Tortajada M, Roura S, G昣lvez-Montón C, et al. Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: Implications for nanomedicine[J]. Theranostics, 2017, 7(2): 270-284.
[24] Chen W, Huang Y, Han J, et al. Immunomodulatory effects of mesenchymal stromal cells-derived exosome[J]. Immunol Res, 2016, 64(4): 831-840.
[25] Zhang B, Yin Y, Lai RC, et al. Mesenchymal stem cells secrete immunologically active exosomes[J]. Stem Cell Dev, 2014, 23(11): 1233-1244.
[26] Ghosh D, McGrail DJ, Dawson MR.TGF-β1 pretreatment improves the function of mesenchymal stem cells in the wound bed[J]. Front Cell Dev Biol, 2017, 5: 28.
[27] De Luca L, Trino S, Laurenzana I, et al. Mesenchymal stem cell derived extracellular vesicles: A role in hematopoietic transplantation?[J]. Int J Mol Sci, 2017, 18(5).
[28] B?rger V, Bremer M, Ferrer-Tur R, et al. Mesenchymal stem/stromal cell-derived extracellular vesicles and their potential as novel immunomodulatory therapeutic agents[J]. Int J Mol Sci, 2017, 18(7).
[29] Sokolova V, Ludwig AK, Hornung S, et al. Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy[J]. Colloid Surf B Biointerface, 2011, 87(1): 146-150.