Abstract
We have investigated the expression of RNA transcripts of hematopoiesis regulatory molecules, viz., macrophage inflammatory protein (MIP)-1α, tumor necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF), stromal cell-derived factor (SDF)-1α, stem cell factor (SCF), and transforming growth factor (TGF)-β in lipopolysaccharide-induced bone marrow mesenchymal stem cells (BM-MSCs) and levels of their soluble forms in the culture supernatants of BM-MSCs and BM plasma of patients with acquired aplastic anemia (AA) (n = 29) and controls (n = 29). The BM-MSCs of AA patients as compared to controls had markedly lower expression of MIP-1α transcripts (p < 0.001), higher expression of TNF-α (p < 0.001), G-CSF (p < 0.001), and SDF-1α (p < 0.01) transcripts, and no difference in the expression of SCF and TGF-β transcripts. The culture supernatants of BM-MSCs and BM plasma of AA patients in comparison to controls also had lower levels of MIP-1α (p < 0.01 and p < 0.001, respectively) and higher levels of TNF-α (p < 0.05 for both) and G-CSF (p < 0.05 and p < 0.001, respectively) but with no difference in the levels of SDF-1α and SCF. The levels of TGF-β were although similar in culture supernatants of BM-MSCs of both the groups, but they were significantly lower in BM plasma of the patients than controls (p < 0.001). Our data shows that BM-MSCs of AA patients have altered expression of hematopoiesis regulatory molecules suggesting that they may have a role in the pathogenesis of the disease.
Highlights
Acquired aplastic anemia (AA) is a state of bone marrow failure characterized by peripheral pancytopenia and a hypoplastic bone marrow (BM) where the normal hematopoietic cells are replaced by fat cells
The BM mesenchymal stem cells (BM-MSCs) of AA patients showed fibroblast-like spindle-shaped morphology similar to BM-MSCs of controls
The oil red O staining of the adipocytes differentiated from AA BM-MSCs showed higher density and larger size of lipid droplets suggesting a higher adipogenic potential of AA BM-MSCs as compared to control BM-MSCs (Figure 1(b))
Summary
Acquired aplastic anemia (AA) is a state of bone marrow failure characterized by peripheral pancytopenia and a hypoplastic bone marrow (BM) where the normal hematopoietic cells are replaced by fat cells. BM mesenchymal stem cells (BM-MSCs) and their differentiated cells constitute the hematopoietic niche in the BM and have a vital role in maintaining long-term hematopoiesis [2].We and other groups have reported an increased adipogenic and/or decreased osteogenic differentiation potential of BM-MSCs in AA patients [3,4,5]. An increase in the adipogenesis and a decrease in the osteogenesis in the BM negatively affect hematopoiesis [6, 7], and these alterations in the differentiation potential of BM-MSCs of AA patients may contribute to the deficient hematopoiesis in AA. Since BM-MSCs interact with HSCs mainly by secreting paracrine molecules including cytokines, chemokines, and growth factors to maintain hematopoietic homeostasis [2, 10],
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