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.
Highlights
Aplastic anemia (AA) is generally considered as an immunemediated bone marrow failure syndrome, characterized by hypoplasia and pancytopenia with fatty bone marrow
We investigated the differences in morphology, immunophenotype markers, proliferation, differentiation, colony-forming unit-fibroblast (CFU-F) and apoptosis of bone marrow mesenchymal stem cells (BM-MSCs) between AA patients and healthy controls
We demonstrated that BM-MSCs from AA patients were multiply defective in biological properties, which were consistent with the differential gene expression profile
Summary
Aplastic anemia (AA) is generally considered as an immunemediated bone marrow failure syndrome, characterized by hypoplasia and pancytopenia with fatty bone marrow. Previous investigations have demonstrated that AA manifests as abnormalities of hematopoietic stem cells (HSCs) and the hematopoietic microenvironment, which are mediated by aberrant immune cells and molecules [1,2]. Aberrant immune cells directly and indirectly destroy stem/progenitor cells in the bone marrow by secreting a variety of immune molecules including interferon-gamma (IFN-c), tumor necrosis factor-alpha (TNF-a) and interleukins (ILs) in AA [3,4,5]. There is increasing evidence suggesting that AA might be a syndrome characterized by stem/progenitor-cell disorders including HSCs and bone marrow mesenchymal stem cells (BM-MSCs). Using clonogenic cultures in vitro, AA manifests as a bone marrow failure syndrome with marked reduction of various subpopulations of HSCs and common myeloid progenitors [6,7,8,9]. Consistent with the above, gene expression profile of CD34+ cells from AA patients identified a large number of different genes expression, which belong mainly to: immune response, apoptosis, cell cycle and proliferation [14]
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