Chemotaxis-Related Factors Are Dysregulated In Bone Marrow Mesenchymal Stem Cells (MSCs) In Multiple Myeloma Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5010-5010
Author(s):  
Hua Lu ◽  
Huijin Hu ◽  
Xiaoming Fei ◽  
Jianyong Li
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mrna Expression ◽  
Mrna Expression Level ◽  
Related Factors ◽  
Expression Levels ◽  
Marrow Mesenchymal Stem Cells ◽  
The Mean ◽  
Mrna Expression Levels

Abstract Abstract 5010 Abstract Objective: This study was aimed to investigate the mRNA expression levels of hepatocyte growth factor(HGF), stromal-derived factor-1(SDF-1), Chemokine (C-C motif) ligand 2 (CCL2) and interleukin-8(IL-8) in bone marrow mesenchymal stem cells (MSC) from multiple myeloma (MM) patients. Methods: The real time quantitative polymerase chain reaction(RQ-PCR)technique was used to detect the mRAN expression levels of HGF, SDF-1, CCL2 and IL-8 in bone marrow MSC from 20 newly diagnosed MM patients compared with 9 controls. Results: The results indicated that the mean mRNA expression level of HGF was up-regulated in MM patients, as compared with control (P < 0.01). However, the mean mRNA expression level of SDF-1 mRNA was down-regulated in MM patients, as compared with control (P < 0.05). There was no significant difference in the mRNA expression levels of CCL2 and IL-8 between MM and control cohorts (P > 0.05). Conclusion: The research suggests that multiple chemotaxis-related factors expression of bone marrow microenvironment cellular component are dysrelugulated in MM patients, which might result from the interplay between MM cell and MSC. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effects of Concentrated Growth Factor on the Proliferation, Migration, and Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells: An in vitro study

2020 ◽  
Author(s):  
Xiang Yu ◽  
Hui Ren ◽  
Qi Shang ◽  
Gengyang Shen ◽  
Kai Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Osteogenic Differentiation ◽  
Control Group ◽  
Elisa Assay ◽  
Alizarin Red ◽  
Expression Levels ◽  
Marrow Mesenchymal Stem Cells ◽  
Mrna Expression Levels

Abstract Background Concentrated growth factor (CGF) has been reported to be effective in bone formation or soft/hard tissue healing in recent years. Despite a few studies regarding the effects of CGF on the proliferation, migration, and osteogenic differentiation of BMSCs, their underlying mechanisms are not fully understood. The purpose of this study is to investigate the effects and possible mechanisms of CGF on the proliferation, migration, and osteogenic differentiation of rat-derived bone marrow mesenchymal stem cells (BMSCs) in vitro. Methods CGF was extracted from the Sprague Dawley (SD) rats by venipuncture of the abdominal aortic vein, and scanning electron microscopy (SEM) was used for the structural characterization. The release of bone morphogenetic protein 2 (BMP-2) from CGF was measured over the periods of 1 ~ 14 days, using the enzyme-linked immunosorbent (Elisa) assay. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. Migration capacity was analyzed using the transwell assay. The osteogenic differentiation and mineralization ability were determined by Alkaline phosphatase activity (ALP) staining and Alizarin Red staining respectively. Quantitative real-time PCR (RT-qPCR), was used to evaluate the mRNA expression levels of Runx2, Ocn, Smad1, and Smad5 after culture for 14 days. Further, the protein expression of BMP-2, phosphorylated-Smad1/5 (p-Smad1/5), and Smad1/5/8 was determined by Western blot after a 14-day cell culture. Results The SEM analysis showed a porous and dense three-dimensional fibrin network in CGF. The Elisa assay showed that BMP-2 was released from CGF extract for more than 14d, and it reached a peak at the time point of 5d. The cell densities of the CGF group at the different concentrations (5%, 10%, and 20%) were significantly higher than that of the control group at the periods of day 1 to day 5 (p < 0.05). Moreover, the number of migratory cells of the CGF group was greater than that of the control group at 24 h. ALP activity analysis and Alizarin Red staining results demonstrated that CGF may successfully induce osteogenic differentiation of BMSCs. Moreover, the RT-qPCR results showed that CGF extracts dramatically enhanced the mRNA expression levels of Runx2, Ocn, Smad1, and Smad5 in BMSCs at days 14 (p < 0.05). Furthermore, Western blot results showed that CGF extracts markedly up-regulated the protein expression levels of BMP-2, p-Smad1/5, and Smad1/5/8. Conclusions CGF can promote the proliferation, migration, and promote the osteogenic differentiation potential of BMSCs in vitro. The BMP-2/Smad signaling pathway was involved in the osteogenic differentiation and mineralization of BMSCs induced by CGF. Therefore, CGF has good application potential in tissue engineering for bone regeneration and repair.

scholarly journals Prognostic significance of Wilms tumor 1 mRNA expression levels in peripheral blood and bone marrow in patients with myelodysplastic syndromes

2016 ◽  
Vol 17 (1) ◽  
pp. 21-32 ◽  
Author(s):  
Sumiko Kobayashi ◽  
Yasunori Ueda ◽  
Yasuhito Nannya ◽  
Hirohiko Shibayama ◽  
Hideto Tamura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mrna Expression ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Wilms Tumor ◽  
Prognostic Significance ◽  
Expression Levels ◽  
Wilms Tumor 1 ◽  
Mrna Expression Levels

Upregulation of TRAIL in Myeloma Cells Correlates with Skeletal-Related Events.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2844-2844
Author(s):  
Yawara Kawano ◽  
Shikiko Ueno ◽  
Yutaka Okuno ◽  
Yoshitaka Kikukawa ◽  
Hiroaki Mitsuya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mrna Expression ◽  
Pathological Fracture ◽  
Trail Expression ◽  
Expression Levels ◽  
Skeletal Complications ◽  
Skeletal Related Events ◽  
Fracture Bone ◽  
Induced Apoptosis ◽  
Mrna Expression Levels

Abstract Abstract 2844 Poster Board II-820 Introduction: Skeletal complications including bone fracture, bone pain and hypercalcemia are major clinical events in patients of multiple myeloma (MM). Osteoclastgenesis is known to be induced by free receptor activator of nuclear factor kappa β ligand (RANKL) and inhibited by dimerization of RANKL and osteoprotegerin (OPG). OPG is also known as a soluble inhibitor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); therefore, a possible role of TRAIL as an osteoclast inducer is suggested, although the association of TRAIL with bone lesions in MM is a matter of debate. We thus investigated the expression of TRAIL mRNA in purified MM cells and analyzed its association with skeletal-related events. Patients and Methods: MM cells were purified from bone marrow samples from 40 MM patients by CD138-immunomagnetic beads (Miltenyi Biotech, Paris, France). TRAIL mRNA expression in purified MM cells was analyzed by real time PCR(ABI PRISM 7700 Sequence Detector, Applied Biosystems). Simultaneous analysis of serum TRAIL concentrations, analyzed by ELISA (Diaclone, Cedex, France), and TRAIL mRNA-expression levels was also performed in 23 cases. Each of these patients was given a score called skeletal-related event score (SRE score) according to the skeletal complications (pathological fracture, bone-associated plasmacytoma, >12mg/dL hypercalcemia, and receiving an pathological fracture-related operation or radiation therapy). Results: Significant association (p=0.0006) was seen between TRAIL mRNA expression levels and the SRE score (Fig.1). Serum calcium levels also had significant association to TRAIL mRNA expression levels (p=0.0050). On the other hand, no association of TRAIL mRNA with hemoglobin (p=0.3970) and platelets (p=0.9401) was seen. Serum TRAIL concentrations in MM cases, which were equivalent to those in healthy individuals, did not correlate to TRAIL mRNA expression levels in purified MM cells (p=0.4094). Conclusions: The data suggest that MM patients with high TRAIL expression in MM cells tend to have more skeletal complications, which may be mediated by increased osteoclastgenesis. Since serum TRAIL concentrations did not correlate with TRAIL mRNA levels in MM cells, increased TRAIL expression in bone marrow microenvironment could be important. Despite of previous reports suggesting TRAIL-induced apoptosis of hematopoietic cells, the observed high TRAIL expression did not correlate with anemia or thrombocytopenia in our cases. Although mechanisms regulating TRAIL expression in MM cells and protection from TRAIL-induced apoptosis remain to be determined, our findings may introduce a new strategy targeting TRAIL to reduce skeletal events in MM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The siRNA-mediated knockdown of GluN3A in 46C-derived neural stem cells affects mRNA expression levels of neural genes, including known iGluR interactors

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192242
Author(s):  
Svenja Pachernegg ◽  
Sebastian Eilebrecht ◽  
Elke Eilebrecht ◽  
Hendrik Schöneborn ◽  
Sebastian Neumann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Mrna Expression ◽  
Expression Levels ◽  
Neural Genes ◽  
Mrna Expression Levels

scholarly journals Multiple myeloma cells promote migration of bone marrow mesenchymal stem cells by altering their translation initiation

2016 ◽  
Vol 100 (4) ◽  
pp. 761-770 ◽  
Author(s):  
Mahmoud Dabbah ◽  
Oshrat Attar-Schneider ◽  
Victoria Zismanov ◽  
Shelly Tartakover Matalon ◽  
Michael Lishner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Translation Initiation ◽  
Myeloma Cells ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Th2 cytokine bias induced by silver nanoparticles in peripheral blood mononuclear cells of common bottlenose dolphins (Tursiops truncatus)

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5432 ◽  
Author(s):  
Wen-Ta Li ◽  
Lei-Ya Wang ◽  
Hui-Wen Chang ◽  
Wei-Cheng Yang ◽  
Chieh Lo ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Bottlenose Dolphins ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Expression Levels ◽  
Th2 Cytokine ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mrna Expression Levels

Background Silver nanoparticles (AgNPs) have been widely used in many commercial products due to their excellent antibacterial ability. The AgNPs are released into the environment, gradually accumulate in the ocean, and may affect animals at high trophic levels, such as cetaceans and humans, via the food chain. Hence, the negative health impacts caused by AgNPs in cetaceans are of concern. Cytokines play a major role in the modulation of immune system and can be classified into two types: Th1 and Th2. Th1/Th2 balance can be evaluated by the ratios of their polarizing cytokines (i.e., interferon [IFN]-γ/Interleukin [IL]-4), and animals with imbalanced Th1/Th2 response may become more susceptible to certain kinds of infection. Therefore, the present study evaluated the in vitro cytokine responses of cetacean peripheral blood mononuclear cells (cPBMCs) to 20 nm citrate-AgNPs (C-AgNP20) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Methods Blood samples were collected from six captive common bottlenose dolphins (Tursiops truncatus). The cPBMCs were isolated and utilized for evaluating the in vitro cytokine responses. The cytokines evaluated included IL-2, IL-4, IL-10, IL-12, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. The geometric means of two housekeeping genes (HKGs), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and β2-microglobulin (B2M), of each sample were determined and used to normalize the mRNA expression levels of target genes. Results The ratio of late apoptotic/necrotic cells of cPBMCs significantly increased with or without concanavalin A (ConA) stimulation after 24 h of 10 µg/ml C-AgNP20 treatment. At 4 h of culture, the mRNA expression level of IL-10 was significantly decreased with 1 µg/ml C-AgNP20 treatment. At 24 h of culture with 1 µg/ml C-AgNP20, the mRNA expression levels of all cytokines were significantly decreased, with the exceptions of IL-4 and IL-10. The IFN-γ/IL-4 ratio was significantly decreased at 24 h of culture with 1 µg/ml C-AgNP20 treatment, and the IL-12/IL-4 ratio was significantly decreased at 4 or 24 h of culture with 0.1 or 1 µg/ml C-AgNP20 treatment, respectively. Furthermore, the mRNA expression level of TNF-α was significantly decreased by 1 µg/ml C-AgNP20 after 24 h of culture. Discussion The present study demonstrated that the sublethal dose of C-AgNP20 (≤1 µg/ml) had an inhibitory effect on the cytokine mRNA expression levels of cPBMCs with the evidence of Th2 cytokine bias and significantly decreased the mRNA expression level of TNF-α. Th2 cytokine bias is associated with enhanced immunity against parasites but decreased immunity to intracellular microorganisms. TNF-α is a contributing factor for the inflammatory response against the infection of intracellular pathogens. In summary, our data indicate that C-AgNP20 suppresses the cellular immune response and thereby increases the susceptibility of cetaceans to infection by intracellular microorganisms.

scholarly journals Healing capacity of bone marrow mesenchymal stem cells versus platelet-rich fibrin in tibial bone defects of albino rats: an in vivo study

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1573 ◽  
Author(s):  
Dina Rady ◽  
Rabab Mubarak ◽  
Rehab A. Abdel Moneim
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Defects ◽  
Treated Group ◽  
Platelet Rich Fibrin ◽  
Weight Percentage ◽  
Tibia Bone ◽  
Marrow Mesenchymal Stem Cells ◽  
The Mean

Background: Various techniques for tissue engineering have been introduced to aid the regeneration of defective or lost bone tissue. The aim of this study was to compare the in vivo bone-forming potential of bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich fibrin (PRF) on induced bone defects in rats’ tibiae. Methods: In total, one defect of 3-mm diameter was created in each tibia of 36 Wistar male rats. There were two groups: group A, left tibia bone defects that received PRF; and group B, right tibia bone defects of the same animal that received BM-MSCs loaded on a chitosan scaffold. Subsequently, Scanning electron microscope/energy-dispersive X-ray (SEM/EDX) analyses was performed at 3 and 10 days, and 3 weeks post‑implantation and following euthanasia; (n=12). Results: The EDX analysis performed for each group and time point revealed a significant increase in the mean calcium and phosphorous weight percentage in the BM-MSC-treated group relative to the PRF-treated group at all-time intervals (P < 0.05). Moreover, the mean calcium and phosphorus weight percentage increased as time progressed since the surgical intervention in the PRF-treated and BM-MSCs groups (P < 0.05). Conclusions: In the present study, both BM-MSCs and PRF were capable of healing osseous defects induced in a rat tibial model. Yet, BM-MSCs promoted more adequate healing, with higher mean calcium and phosphorous weight percentages than PRF at all-time points, and showed greater integration into the surrounding tissues than PRF.

scholarly journals The BMP signaling pathway enhances the osteoblastic differentiation of bone marrow mesenchymal stem cells in rats with osteoporosis

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Bin Zhao ◽  
Gengyan Xing ◽  
Aiyuan Wang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Adipogenic Differentiation ◽  
Osteoblastic Differentiation ◽  
Bmp Signaling ◽  
Blank Group ◽  
Expression Levels ◽  
Marrow Mesenchymal Stem Cells

Abstract Background This study was conducted with the aim of exploring the effect of the BMP signaling pathway on osteoblastic differentiation in rat bone marrow mesenchymal stem cells (rBMSCs) in rats with osteoporosis (OP). Methods The bilateral ovaries of female SD rats were resected for the establishment of a rat OP model. The osteoblastic differentiation of isolated rBMSCs was identified through osteogenic induction. Adipogenetic induction and flow cytometry (FCM) were used to detect adipogenic differentiation and the expression of rBMSC surface markers. The rBMSCs were grouped into the blank group, NC group, si-BMP2 group, and oe-BMP2 group. The expression levels of key factors and osteogenesis-related factors were determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The formation of calcified nodules was observed by alizarin red staining. ALP activity was measured by alkaline phosphatase staining. Results The rats with OP had greater weight but decreased bone mineral density (BMD) than normal rats (all P < 0.01). The rBMSCs from rats with OP were capable of osteoblastic differentiation and adipogenic differentiation and showed high expression of CD44 (91.3 ± 2.9%) and CD105 (94.8 ± 2.1%). Compared with the blank group, the oe-BMP2 group had elevated BMP-2 and Smad1 levels and an increase in calcified nodules and ALP-positive staining areas (all P < 0.05). Moreover, the expression levels of Runx2, OC, and OPN in the oe-BMP2 group were relatively higher than those in the blank group (all P < 0.05). The findings in the si-BMP2 group were opposite to those in the oe-BMP2 group. Conclusion BMP signaling pathways activated by BMP-2 can promote the osteoblastic differentiation of rBMSCs from rats with OP.

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