骨髓间充质干细胞缺陷与获得性再生障碍性贫血

章婧嫽, 竺晓凡

中国当代儿科杂志 ›› 2015, Vol. 17 ›› Issue (1) : 100-106.

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中国当代儿科杂志 ›› 2015, Vol. 17 ›› Issue (1) : 100-106. DOI: 10.7499/j.issn.1008-8830.2015.01.024
综述

骨髓间充质干细胞缺陷与获得性再生障碍性贫血

  • 章婧嫽, 竺晓凡
作者信息 +

Defectiveness of bone marrow mesenchymal stem cells in acquired aplastic anemia

  • ZHANG Jing-Liao, ZHU Xiao-Fan
Author information +
文章历史 +

摘要

获得性再生障碍性贫血(AA)患者骨髓间充质干细胞(BM-MSCs)缺陷已成为近年来研究的热点之一.该文对BM-MSCs 缺陷在AA 发病中的作用及其对AA 治疗的临床应用进行综述.越来越多的实验室证据证明了BM-MSCs 缺陷在AA 的发病中极有可能起着重要的作用,无论是其生物学特点、基因表达谱的缺陷,抑或是增殖分化能力、造血支持作用乃至免疫调节功能的耗竭,都成为在免疫失衡基础上促使AA 不断进展至难以恢复的重要节点.随着MSCs 研究的不断深化,将恢复骨髓造血微环境为主要目的的MSCs 输注可能成为AA 治疗的新模式.

Abstract

The defectiveness of bone marrow mesenchymal stem cells (BM-MSCs) in acquired aplastic anemia (AA) has been a frequent research topic in recent years. This review summarizes the defectiveness of BM-MSCs which is responsible for the mechanism of acquired AA and the prospective application of BM-MSCs in the treatment of acquired AA. An increasingly number of laboratory statistics has demonstrated that the defectiveness of BM-MSCs is more likely to play an important role in the pathogenesis of AA, namely, the apparently different biological characteristics and gene expression profiles, the decreased ability of supporting hematopoiesis as well as self-renewal and differentiation, and the exhaustion of regulating immune response of hematopoietic environment. Those abnormalities continuously prompt AA to become irreversible bone marrow failure along with the imbalanced immunity. With deepening research on MSCs, infusion of MSCs for the primary purpose of recovering hematopoietic microenvironment may become a new approach for the treatment of AA.

关键词

获得性再生障碍性贫血 / 骨髓间充质干细胞 / 缺陷

Key words

Acquired aplastic anemia / Bone marrow mesenchymal stem cell / Defectiveness

引用本文

导出引用
章婧嫽, 竺晓凡. 骨髓间充质干细胞缺陷与获得性再生障碍性贫血[J]. 中国当代儿科杂志. 2015, 17(1): 100-106 https://doi.org/10.7499/j.issn.1008-8830.2015.01.024
ZHANG Jing-Liao, ZHU Xiao-Fan. Defectiveness of bone marrow mesenchymal stem cells in acquired aplastic anemia[J]. Chinese Journal of Contemporary Pediatrics. 2015, 17(1): 100-106 https://doi.org/10.7499/j.issn.1008-8830.2015.01.024

参考文献

[1] Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia[J]. Blood, 2006, 108(8): 2509-2519.
[2] Li JP, Zheng CL, Han ZC. Abnormal immunity and stem/progenitor cells in acquired aplastic anemia[J]. Crit Rev Oncol Hematol, 2010, 75(2): 79-93.
[3] Zoumbos NC, Gascon P, Djeu JY, et al. Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo[J]. Proc Natl Acad Sci U S A., 1985, 82(1): 188-192.
[4] Verma A, Deb DK, Sassano A, et al. Cutting edge: activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia[J]. J Immunol, 2002, 168(12): 5984-5988.
[5] Sloand E, Kim S, Maciejewski JP, et al. Intracellular interferon-γ in circulating and marrow T cells detected by flow cytometry and the response to immunosuppressive therapy in patients with aplastic anemia[J]. Blood, 2002, 100(4): 1185-1191.
[6] Zeng W, Chen G, Kajigaya S, et al. Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers[J]. Blood, 2004, 103(1): 325-332.
[7] Young NS, Bacigalupo A, Marsh JCW. Aplastic anemia: pathophysiology and treatment[J]. Biol Blood Marrow Transplant, 2010, 16(1): S119-S125.
[8] 吴艳, 于洁, 张磊, 等. 再生障碍性贫血患儿骨髓间充质干 细胞体外造血支持作用的研究[J]. 中国当代儿科杂志, 2008, 10(4): 455-459.
[9] 张乐玲, 李府, 吴镇, 等. 再生障碍性贫血患儿骨髓间充质 干细胞免疫调节特性和造血支持作用的研究[J]. 中国小儿血 液与肿瘤杂志, 2008, 13(4): 145-148.
[10] 陈新, 华建媛, 石庆之. 人脐带间充质干细胞对再生障碍性 贫血 T 细胞的调节作用[J]. 中国组织工程研究与临床康复, 2009, 13(40): 7908-7912.
[11] Li JP, Lu SH, Yang SG, et al. Impaired immunomodulatory ability of bone marrow mesenchymal stem cells on CD4+ T cells in aplastic anemia[J]. Results Immunol, 2012, 2: 142-147.
[12] Li J, Yang S, Lu S, et al. Differential gene expression profile associated with the abnormality of bone marrow mesenchymal stem cells in aplastic anemia[J]. PloS One, 2012, 7(11): e47764.
[13] De Lima M, McNiece I, Robinson SN, et al. Cord-blood engraftment with ex vivo mesenchymal cell coculture[J]. N Engl J Med, 2012, 367: 2305e15.
[14] Bernardo ME, Fibbe WE. Safety and efficacy of mesenchymal stromal cell therapy in autoimmune disorders[J]. Ann N Y Acad Sci, 2012, 1266(1): 107-117.
[15] Nimer SD, Leung DH, Wolin MJ, et al. Serum stem cell factor levels in patients with aplastic anemia[J]. Int J Hematol, 1994, 60(3): 185-189.
[16] 杨诗梅, 陆世丰, 费小明, 等. 骨髓衰竭患者骨髓间充质干 细胞细胞因子的表达变化及其意义[J]. 中国实验血液学杂 志, 2010, 18(6): 1560-1563.
[17] Kojima S, Matsuyama T, Kodera Y. Plasma levels and production of soluble stem cell factor by marrow stromal cells in patients with aplastic anaemia[J]. Br J Haematol, 1997, 99(2): 440-446.
[18] 刘双, 滕清良. VEGF, bFGF 在再生障碍性贫血患者骨髓中 的表达及意义[J]. 山东医药, 2009, 49(11): 44-45.
[19] Chen YF, Wu ZM, Xie C, et al. Expression level of IL-6 secreted by bone marrow stromal cells in mice with aplastic anemia[J]. ISRN Hematol, 2013, 2013: 986219.
[20] 管英华, 谢杨虎, 魏晓巍, 等. 骨髓间充质干细胞与再生障 碍性贫血的研究进展[J]. 中华全科医学, 2012, 10(7): 1131-1132.
[21] Di Maggio N, Mehrkens A, Papadimitropoulos A, et al. Fibroblast growth factor-2 maintains a niche-dependent population of self-renewing highly potent non-adherent mesenchymal progenitors through FGFR2c[J]. Stem Cells, 2012, 30(7): 1455-1464.
[22] Jiang SY, Xie XT, Jiang H, et al. Low expression of basic fibroblastic growth factor in mesenchymal stem cells and bone marrow of children with aplastic anemia[J]. Pediatr Hematol Oncol, 2014, 31(1): 11-19.
[23] Liu L, Sun Z, Han Q, et al. T-cell suppression mediated by mesenchymal stem cells in patients with chronic aplastic anemia[J]. Basic Clin Med, 2007, 27(9): 1006-1010.
[24] 黄永兰, 黄绍良, 黄科, 等. 再生障碍性贫血患儿骨髓间充 质干细胞体外生物学特性及其与免疫抑制疗效的关系[J]. 中 国当代儿科杂志, 2008, 10(1): 9-13.
[25] Chao YH, Peng CT, Harn HJ, et al. Poor potential of proliferation and differentiation in bone marrow mesenchymal stem cells derived from children with severe aplastic anemia[J]. Ann Hematol, 2010, 89(7): 715-723.
[26] El-Mahgoub ER, Ahmed E, Afifi RAEA, et al. Mesenchymal stem cells from pediatric patients with aplastic anemia: isolation, characterization, adipogenic, and osteogenic differentiation[J]. Fetal Pediatr Pathol, 2014, 33(1): 9-15.
[27] 程梅, 张颢, 陶艳玲, 等. 成人再生障碍性贫血患者骨髓间 充质干细胞增殖分化潜能: 与健康人的比较[J]. 中国组织工 程研究, 2012, 16(32): 5936-5940.
[28] Gurevitch O, Slavin S, Resnick I, et al. Mesenchymal progenitor cells in red and yellow bone marrow[J]. Folia Biol (Praha), 2009, 55(1): 27-34.
[29] 岳寒, 陈磊, 李静, 等. 再生障碍性贫血患者骨髓间充质干 细胞生物学特性的初步研究[J]. 中国生物工程杂志, 2005, 25(6): 20-24.
[30] Tripathy NK, Singh SP, Nityanand S. Enhanced adipogenicity of bone marrow mesenchymal stem cells in aplastic anemia[J]. Stem Cells In, 2014, 2014: 276862.
[31] Xu Y, Takahashi Y, Wang Y, et al. Downregulation of GATA-2 and overexpression of adipogenic gene PPARgamma in mesenchymal stem cells from patients with aplastic anemia[J]. Exp Hematol, 2009, 37(12): 1393-1399
[32] Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size[J]. Nature, 2003, 425(6960): 836-841.
[33] Visnjic D, Kalajzic Z, Rowe DW, et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency[J]. Blood, 2004, 103(9): 3258-3264.
[34] 李建平, 杨少光, 卢世红 等. 再生障碍性贫血患者骨髓间 充质干细胞对 CD4+ 细胞功能的影响[J]. 青海医学院学报, 2012, 33(4): 217-223.
[35] Bacigalupo A, Valle M, Podestà M, et al. T-cell suppression mediated by mesenchymal stem cells is deficient in patients with severe aplastic anemia[J]. Exp Hematol, 2005, 33(7): 819-827.
[36] Xu Y, Takahashi Y, Yoshimi A, et al. Immunosuppressive activity of mesenchymal stem cells is not decreased in children with aplastic anemia[J]. Int J Hematol, 2009, 89(1): 126-127.
[37] Kordasti S, Marsh J, Al-Khan S, et al . Functional characterization of CD4+ T cells in aplastic anemia[J]. Blood, 2012, 119(9): 2033-2043.
[38] Guo Z, Zheng C, Chen Z, et al. Fetal BM-derived mesenchymal stem cells promote the expansion of human Th17 cells, but inhibit the production of Th1 cells[J]. Eur J Immunol, 2009, 39(10): 2840-2849.
[39] Chen K, Wang D, Du WT, et al. Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism[J]. Clin Immunol, 2010, 135(3): 448–458.
[40] Gieseke F, Bohringer J, Bussolari R, et al. Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells[J]. Blood, 2010, 116 (19): 3770–3779.
[41] Gebler A, Zabel O, Seliger B. The immunomodulatory capacity of mesenchymal stem cells[J]. Trends Mol Med, 2012, 18(2): 128-134.
[42] Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation[J]. Annu Rev Pathol, 2011, 6: 457-478..
[43] Jaganathan BG, Tisato V, Vulliamy T, et al. Effects of MSC co-injection on the reconstitution of aplastic anemia patient following hematopoietic stem cell transplantation[J]. Leukemia, 2010, 24(10): 1791-1795.
[44] Wang H, Wang Z, Xue M, et al. Co-transfusion of haploidentical hematopoietic and mesenchymal stromal cells to treat a patient with severe aplastic[J]. Cytotherapy, 2010, 12(4): 563-565.
[45] Chao YH, Tsai C, Peng CT, et al. Cotransplantation of umbilical cord MSCs to enhance engraftment of hematopoietic stem cells in patients with severe aplastic anemia[J]. Bone Marrow Transp, 2011, 46(10): 1391-1392.
[46] Wang H, Yan H, Wang Z, et al. Cotransplantation of allogeneic mesenchymal and hematopoietic stem cells in children with aplastic anemia[J]. Pediatrics, 2012, 129(6): e1612-1615.
[47] de Latour RP, Visconte V, Takaku T, et al. Th17 immune responses contribute to the pathophysiology of aplastic anemia[J]. Blood, 2010, 116(20): 4175-4184 .
[48] Scheinberg P, Young NS. How I treat acquired aplastic anemia[J]. Blood, 2012, 120(6): 1185-1196
[49] Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells[J]. Nature, 2006, 441(7090): 235-238.
[50] Yan Z, Zhuansun Y, Chen R, et al. Immunomodulation of mesenchymal stromal cells on regulatory T cells and its possible mechanism[J]. Exp Cell Res, 2014, 324(1): 65-74.
[51] Zhang B, Yin Y, Lai RC, et al. Mesenchymal stem cell secretes immunologically active exosomes[J]. Stem Cells Dev, 2014, 23(11): 1233-1244.
[52] 柴晔, 刘瑛, 孙媛媛, 等. 人脐带间充质干细胞对再生障 碍性贫血患者 Treg 细胞的影响[J]. 中国免疫学杂志, 2012, 27(9): 837-839.
[53] 刘增慧, 肖扬, 蒋祖军, 等. 骨髓间充质干细胞上调再生障 碍性贫血患者 CD4+ CD25+ Foxp3+ 调节性 T 细胞的临床研究[J]. 实用医学杂志, 2011, 27(9): 1582-1585.
[54] Bueno C, Roldan M, Anguita E, et al. Bone marrow mesenchymal stem cells from aplastic anemia patients preserve functional and immune properties and do not contribute to the pathogenesis of the disease[J]. Haematologica, 2014, 99(7): 1168-1175.
[55] Si Y, Yang K, Qin M, et al. Efficacy and safety of human umbilical cord derived mesenchymal stem cell therapy in children with severe aplastic anemia following allogeneic hematopoietic stem cell transplantation: a retrospective case series of 37 patients[J]. Pediatr Hematol Oncol, 2014, 31(1): 39-49.
[56] 徐丽昕, 曹永彬, 王志红, 等. 单倍体相合造血干细胞联合 脐带血间充质干细胞移植治疗急性重型再生障碍性贫血的 疗效观察[J]. 中国实验血液学杂志, 2011, 19(5): 1241-1245.
[57] 闫洪敏, 王志东, 朱玲, 等. 多种来源造血干细胞移植治疗 重型再生障碍性贫血[J]. 中国组织工程研究, 2011, 15(10): 1884-1888.
[58] Kim EJ, Kim N, Cho SG. The potential use of mesenchymal stem cells in hematopoietic stem cell transplantation[J]. Exp Mol Med, 2013, 45(1): e2.

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