Bone Marrow Research最新文献

S100A8 and S100A9 are both members of the S100 family and have been shown to play roles in myeloid differentiation, autophagy, apoptosis, and chemotherapy resistance. In this study we demonstrate that the BET-bromodomain inhibitor JQ1 causes rapid suppression of S100A8 and S100A9 mRNA and protein in a reversible manner. In addition, we show that JQ1 synergises with daunorubicin in causing AML cell death. Daunorubicin alone causes a dose- and time-dependent increase in S100A8 and S100A9 protein levels in AML cell lines which is overcome by cotreatment with JQ1. This suggests that JQ1 synergises with daunorubicin in causing apoptosis via suppression of S100A8 and S100A9 levels.

There is great variation in cytopenias in cirrhotic patients with same severity and hypersplenism and their causative factors are not clear. Recent studies have highlighted the role of gut microbiome in regulation of constant and emergency hematopoiesis. Broad-spectrum antibiotics can disrupt the homeostatic or adaptive microbiota in cirrhosis, leading to impaired hematopoiesis and a higher susceptibility to infections. We studied all patients with cirrhosis with cytopenia (anemia, leucopenia, and/or thrombocytopenia), admitted in the Institute of Liver & Biliary Sciences, between January 2016 and July 2017, who underwent a bone marrow examination. The effect of the different antimicrobial agents on peripheral blood counts and bone marrow cellularity was assessed. A total of 196 patients' data was analyzed for this study. Patients on antimicrobials (n = 115) had significantly lower hemoglobin (p < 0.001), total leucocyte count (p = 0.048), and platelet count (p = 0.043) compared to patients not on antimicrobials. On unadjusted analysis, significant association with thrombocytopenia existed in beta-lactams (OR = 1.56, 95% CI = 1.06-2.40), quinolones (OR = 1.66, 95% CI = 1.11-2.61), and antifungals (OR = 2.24, 95% CI = 1.96-4.34). Cephalosporins were found to be significantly associated with anemia (OR = 1.91, 95% CI = 1.07-3.41). Patients who received antimicrobials had hypocellular marrow (p < 0.001) as compared to nonrecipients of antibiotics. The adjusted analysis showed that quinolones and beta-lactam antibiotics are the drug classes having significant association with thrombocytopenia and alternative class of drug should be explored in these patients to avoid severe thrombocytopenia.

The purpose of this study was to quantify the stem cell and growth factor (GF) contents in the bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) prepared from whole blood using a protocol established in our laboratory. We examined 10 patients with osteonecrosis of the femoral head who were treated by autologous BMAC transplantation at our hospital between January 2015 and June 2015. We quantified CD34+ and CD31-CD45-CD90+CD105+ cells in BMAC and PRP by flow cytometry. Additionally, we measured various GFs, that is, basic fibroblast growth factor (b-FGF), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and bone morphogenetic protein-2 (BMP-2) in BMAC and PRP using enzyme-linked immunosorbent assays and statistical analyses. CD34+ and CD31-45-90+105+ cells accounted for approximately 1.9% and 0.03% of cells in BMAC and no cells in PRP. The concentration of b-FGF was higher in BMAC than in PRP (P < 0.001), whereas no significant differences in the levels of PDGF-BB, VEGF, TGF-β1, and BMP-2 were observed between the two types of sample. BMAC had an average of 1.9% CD34+ and 0.03% CD31-45-90+105+ cells and higher levels of b-FGF than those of PRP.

12-14 days of culturing of bone marrow (BM) cells containing various growth factors is widely used method for generating dendritic cells (DCs) from suspended cell population. Here we compared flask culture method and commercially available CD11c Positive Selection kit method. Immature BMDCs' purity of adherent as well as suspended cell population was generated in the decreasing concentration of recombinant-murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) in nontreated tissue culture flasks. The expression of CD11c, MHCII, CD40, and CD86 was measured by flow cytometry. We found significant difference (P < 0.05) between the two methods in the adherent cells population but no significant difference was observed between the suspended cell populations with respect to CD11c+ count. However, CD11c+ was significantly higher in both adhered and suspended cell population by culture method but kit method gave more CD11c+ from suspended cells population only. On the other hand, using both methods, immature DC expressed moderate level of MHC class II molecules as well as low levels of CD40 and CD86. Our findings suggest that widely used culture method gives the best results in terms of yield, viability, and purity of BMDCs from both adherent and suspended cell population whereas kit method works well for suspended cell population.

Αlpha-solanine (α-solanine) is a glycoalkaloid present in potato (Solanum tuberosum). It has been of particular interest because of its toxicity and potential teratogenic effects that include abnormalities of the central nervous system, such as exencephaly, encephalocele, and anophthalmia. Various types of cell culture have been used as experimental models to determine the effect of α-solanine on cell physiology. The morphological changes in the mesenchymal stem cell upon exposure to α-solanine have not been established. This study aimed to describe a reliable and reproducible model for assessing the structural changes induced by exposure of mouse bone marrow mesenchymal stem cells (MSCs) to different concentrations of α-solanine for 24 h. The results demonstrate that nonlethal concentrations of α-solanine (2-6 μM) changed the morphology of the cells, including an increase in the number of nucleoli, suggesting elevated protein synthesis, and the formation of spicules. In addition, treatment with α-solanine reduced the number of adherent cells and the formation of colonies in culture. Immunophenotypic characterization and staining of MSCs are proposed as a reproducible method that allows description of cells exposed to the glycoalkaloid, α-solanine.

No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30 μg/kg) or saline administration three times per week (n = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy.