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

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.

Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain functional and immune properties and do not contribute to the pathogenesis of the disease

“…In fact, AA patients have a hypocellular BM which is "physiologically" replaced by fatty BM, likely of mesenchymal origin, further supporting a potential contribution of the BM microenvironment to the pathogenesis of AA. 41 MSC have robust immunomodulatory and anti-inflammatory properties [11][12][13] and are an essential component of the BM hematopoietic microenvironment, which regulates the homeostasis of hematopoiesis through the production and secretion of cytokines and extracellular matrix molecules.…”

“…8,[41][42][43][44][45][46][47][48] These studies mainly claim that AA BM-MSC have aberrant morphology, impaired adipogenic and osteogenic potential, changes in gene expression, and a reduced ability to support hematopoiesis in vitro. However, to the best of our knowledge, no study so far has prospectively addressed in depth the ability of AA BM-MSC to maintain hematopoietic homeostasis and progenitor function in vitro, their in vivo repopulating function in xenotransplant models, or the immunosuppressive and anti-inflammatory properties on these cells.…”

“…46 Our data are in partial disagreement with those of other studies suggesting that AA BM-MSC are aberrant. 8,41,42,44,46,48 From a methodological point of view, we assessed the features of AA BM-MSC beyond morphology, gene expression, differentiation potential and proliferation by analyzing the cells' ability to support hematopoiesis in vitro and in vivo and their immune properties. Biologically, all our patients, but one, were elderly patients while other studies focused on chil-BM-MSC in aplastic anemia haematologica | 2014; 99(7) dren/young adults with AA.…”

“…Biologically, all our patients, but one, were elderly patients while other studies focused on chil-BM-MSC in aplastic anemia haematologica | 2014; 99(7) dren/young adults with AA. 41,42 Importantly, there are also several degrees of severity of AA. Our patients were diagnosed as having moderate-severe AA while other studies analyzed patients with very severe AA.…”

Decoy receptor 3 regulates the expression of various genes in rheumatoid arthritis synovial fibroblasts

“…Genome-wide gene expression cDNA microarray is a powerful technique used to investigate the pathophysiology of a variety of diseases, including tumors (28-30), immune-mediated diseases (31,32) and inflammatory diseases (33)(34)(35). Using microarray, Chang et al revealed that genes characteristically expressed by tumor-associated macrophages were upregulated by DcR3 (30).…”