Altered expression of hematopoiesis regulatory molecules in lipopolysaccharide-induced bone marrow mesenchymal stem cells of patients with aplastic anemia

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.