Differential Gene Expression Profile Associated with the Abnormality of Bone Marrow Mesenchymal Stem Cells in Aplastic Anemia

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Nov 13

PMID 23144828

Citations 37

Authors

Jianping Li

Shaoguang Yang

Shihong Lu

Hui Zhao

Jianming Feng

Wenqian Li

Fengxia Ma

Qian Ren

Bin Liu

Lei Zhang

Yizhou Zheng

Zhong Chao Han

Affiliations

Soon will be listed here.

Abstract

Aplastic anemia (AA) is generally considered as an immune-mediated bone marrow failure syndrome with defective hematopoietic stem cells (HSCs) and marrow microenvironment. Previous studies have demonstrated the defective HSCs and aberrant T cellular-immunity in AA using a microarray approach. However, little is known about the overall specialty of bone marrow mesenchymal stem cells (BM-MSCs). In the present study, we comprehensively compared the biological features and gene expression profile of BM-MSCs between AA patients and healthy volunteers. In comparison with healthy controls, BM-MSCs from AA patients showed aberrant morphology, decreased proliferation and clonogenic potential and increased apoptosis. BM-MSCs from AA patients were susceptible to be induced to differentiate into adipocytes but more difficult to differentiate into osteoblasts. Consistent with abnormal biological features, a large number of genes implicated in cell cycle, cell division, proliferation, chemotaxis and hematopoietic cell lineage showed markedly decreased expression in BM-MSCs from AA patients. Conversely, more related genes with apoptosis, adipogenesis and immune response showed increased expression in BM-MSCs from AA patients. The gene expression profile of BM-MSCs further confirmed the abnormal biological properties and provided significant evidence for the possible mechanism of the destruction of the bone marrow microenvironment in AA.

Citing Articles

Up-Regulated Expression of Thioredoxin-Interacting Protein (TXNIP) in Mesenchymal Stem Cells Associated with Severe Aplastic Anemia in Children.

Peng Y, Li C, Wu K, Li J, Yang S, Chao Y Int J Mol Sci. 2024; 25(22).

PMID: 39596362 PMC: 11594798. DOI: 10.3390/ijms252212298.

PDGF-BB Deficiency in the Blood Serum from Aplastic Anemia Patients Affects Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells.

Dorofeeva A, Shipounova I, Nikiforova K, Galtseva I, Kuzmina L, Luchkin A Cells. 2024; 13(22).

PMID: 39594656 PMC: 11592413. DOI: 10.3390/cells13221908.

Global microRNA profiling of bone marrow-MSC derived extracellular vesicles identifies miRNAs associated with hematopoietic dysfunction in aplastic anemia.

Srivastava J, Kundal K, Rai B, Saxena P, Katiyar S, Tripathy N Sci Rep. 2024; 14(1):19654.

PMID: 39179703 PMC: 11343855. DOI: 10.1038/s41598-024-70369-8.

Mesenchymal Stem Cells in Acquired Aplastic Anemia: The Spectrum from Basic to Clinical Utility.

Wang X, Li J, Wu K, Yang S, Chao Y Int J Mol Sci. 2023; 24(5).

PMID: 36901900 PMC: 10003043. DOI: 10.3390/ijms24054464.

Alterations of mesenchymal stem cells on regulating Th17 and Treg differentiation in severe aplastic anemia.

Li J, Wu K, Chao W, Lee Y, Yang S, Chao Y Aging (Albany NY). 2023; 15(2):553-566.

PMID: 36719260 PMC: 9925683. DOI: 10.18632/aging.204500.

References

Marsh J, Ball S, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith E . Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009; 147(1):43-70. DOI: 10.1111/j.1365-2141.2009.07842.x. View

Timeus F, Crescenzio N, Doria A, Foglia L, Linari A, Giaccone M . Flow cytometric evaluation of circulating CD34+ cell counts and apoptotic rate in children with acquired aplastic anemia and myelodysplasia. Exp Hematol. 2005; 33(5):597-604. DOI: 10.1016/j.exphem.2005.02.005. View

Steiner R, Mitchell D, Rao V, Murphy S, Rifkin M, Burk Jr D . Magnetic resonance imaging of bone marrow: diagnostic value in diffuse hematologic disorders. Magn Reson Q. 1990; 6(1):17-34. View

Verma A, Deb D, Sassano A, Kambhampati S, Wickrema A, Uddin S . Cutting edge: activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia. J Immunol. 2002; 168(12):5984-8. DOI: 10.4049/jimmunol.168.12.5984. View

Wang H, Wang Z, Xue M, Liu J, Yan H, Guo Z . Co-transfusion of haplo-identical hematopoietic and mesenchymal stromal cells to treat a patient with severe aplastic. Cytotherapy. 2010; 12(4):563-5. DOI: 10.3109/14653241003695059. View

Manz C, Nissen C, Wodnar-Filipowicz A . Deficiency of CD34+ c-kit+ and CD34+38- hematopoietic precursors in aplastic anemia after immunosuppressive treatment. Am J Hematol. 1996; 52(4):264-74. DOI: 10.1002/(SICI)1096-8652(199608)52:4<264::AID-AJH5>3.0.CO;2-Q. View

Killick S, Cox C, Marsh J, Gordon-Smith E, Gibson F . Mechanisms of bone marrow progenitor cell apoptosis in aplastic anaemia and the effect of anti-thymocyte globulin: examination of the role of the Fas-Fas-L interaction. Br J Haematol. 2001; 111(4):1164-9. DOI: 10.1046/j.1365-2141.2000.02485.x. View

Rasmusson I . Immune modulation by mesenchymal stem cells. Exp Cell Res. 2006; 312(12):2169-79. DOI: 10.1016/j.yexcr.2006.03.019. View

Chen X, Armstrong M, Li G . Mesenchymal stem cells in immunoregulation. Immunol Cell Biol. 2006; 84(5):413-21. DOI: 10.1111/j.1440-1711.2006.01458.x. View

10.

Rizzo S, Scopes J, Elebute M, Papadaki H, Gordon-Smith E, Gibson F . Stem cell defect in aplastic anemia: reduced long term culture-initiating cells (LTC-IC) in CD34+ cells isolated from aplastic anemia patient bone marrow. Hematol J. 2002; 3(5):230-6. DOI: 10.1038/sj.thj.6200187. View

11.

Sloand E, Kim S, Maciejewski J, Tisdale J, Follmann D, Young N . Intracellular interferon-gamma in circulating and marrow T cells detected by flow cytometry and the response to immunosuppressive therapy in patients with aplastic anemia. Blood. 2002; 100(4):1185-91. DOI: 10.1182/blood-2002-01-0035. View

12.

Negendank W, Weissman D, Bey T, de Planque M, Karanes C, Smith M . Evidence for clonal disease by magnetic resonance imaging in patients with hypoplastic marrow disorders. Blood. 1991; 78(11):2872-9. View

13.

Schrezenmeier H, Jenal M, Herrmann F, Heimpel H, Raghavachar A . Quantitative analysis of cobblestone area-forming cells in bone marrow of patients with aplastic anemia by limiting dilution assay. Blood. 1996; 88(12):4474-80. View

14.

Philpott N, Scopes J, Marsh J, Gordon-Smith E, Gibson F . Increased apoptosis in aplastic anemia bone marrow progenitor cells: possible pathophysiologic significance. Exp Hematol. 1995; 23(14):1642-8. View

15.

Zeng W, Kajigaya S, Chen G, Risitano A, Nunez O, Young N . Transcript profile of CD4+ and CD8+ T cells from the bone marrow of acquired aplastic anemia patients. Exp Hematol. 2004; 32(9):806-14. DOI: 10.1016/j.exphem.2004.06.004. View

16.

Chao Y, Peng C, Harn H, Chan C, Wu K . Poor potential of proliferation and differentiation in bone marrow mesenchymal stem cells derived from children with severe aplastic anemia. Ann Hematol. 2010; 89(7):715-23. DOI: 10.1007/s00277-009-0892-6. View

17.

Li J, Lu S, Yang S, Xing W, Feng J, Li W . Impaired immunomodulatory ability of bone marrow mesenchymal stem cells on CD4(+) T cells in aplastic anemia. Results Immunol. 2013; 2:142-7. PMC: 3862346. DOI: 10.1016/j.rinim.2012.07.002. View

18.

Li J, Zhao Q, Xing W, Feng J, Wu H, Li H . Interleukin-27 enhances the production of tumour necrosis factor-α and interferon-γ by bone marrow T lymphocytes in aplastic anaemia. Br J Haematol. 2011; 153(6):764-72. DOI: 10.1111/j.1365-2141.2010.08431.x. View

19.

Zeng W, Chen G, Kajigaya S, Nunez O, Charrow A, Billings E . Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers. Blood. 2003; 103(1):325-32. DOI: 10.1182/blood-2003-02-0490. View

20.

Jaganathan B, Tisato V, Vulliamy T, Dokal I, Marsh J, Dazzi F . Effects of MSC co-injection on the reconstitution of aplastic anemia patient following hematopoietic stem cell transplantation. Leukemia. 2010; 24(10):1791-5. DOI: 10.1038/leu.2010.164. View