scholarly journals Paracrine Effects of Bone Marrow Mononuclear Cells in Survival and Cytokine Expression after 90% Partial Hepatectomy

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Carlos Oscar Kieling ◽  
Carolina Uribe-Cruz ◽  
Mónica Luján López ◽  
Alessandro Bersch Osvaldt ◽  
Themis Reverbel da Silveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Partial Hepatectomy ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Remnant Liver ◽  
Promising Alternative ◽  
Paracrine Effects

Acute liver failure is a complex and fatal disease. Cell-based therapies are a promising alternative therapeutic approach for liver failure due to relatively simple technique and lower cost. The use of semipermeable microcapsules has become an interesting tool for evaluating paracrine effects in vivo. In this study, we aimed to assess the paracrine effects of bone marrow mononuclear cells (BMMC) encapsulated in sodium alginate to treat acute liver failure in an animal model of 90% partial hepatectomy (90% PH). Encapsulated BMMC were able to increase 10-day survival without enhancing liver regeneration markers. Gene expression of Il-6 and Il-10 in the remnant liver was markedly reduced at 6 h after 90% PH in animals receiving encapsulated BMMC compared to controls. This difference, however, was neither reflected by changes in the number of CD68+ cells nor by serum levels of IL6. On the other hand, treated animals presented increased caspase activity and gene expression in the liver. Taken together, these results suggest that BMMC regulate immune response and promote apoptosis in the liver after 90% PH by paracrine factors. These changes ultimately may be related to the higher survival observed in treated animals, suggesting that BMMC may be a promising alternative to treat acute liver failure.

scholarly journals Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2532-2535 ◽  
Author(s):  
S Nakao ◽  
M Yamaguchi ◽  
S Shiobara ◽  
T Yokoi ◽  
T Miyawaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Aplastic Anemia ◽  
Interferon Gamma ◽  
Messenger Rna ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Ifn Gamma ◽  
Exact Test ◽  
Transfusion Independence

Cyclosporine (CyA) therapy has been shown to be effective in some patients with aplastic anemia. In an attempt to characterize aplastic patients likely to benefit from CyA therapy, we examined bone marrow mononuclear cells (BMMC) obtained before therapy from 23 patients with aplastic anemia, who were treated with CyA alone. Expression of four myelosuppressive cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and interferon-gamma (IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1 alpha was readily detectable at variable levels in BMMC from normal and transfused controls as well as in BMMC from aplastic patients. In contrast, IFN-gamma mRNA was only demonstrable in BMMC from some patients with aplastic anemia, irrespective of a history of transfusions. Of 13 patients who responded to CyA therapy and achieved transfusion-independence, IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only detectable in 3 of 10 patients refractory to CyA therapy (P = .003, Fisher's exact test). Follow-up examination of BMMC obtained from seven CyA-responding patients after hematologic remission showed disappearance of IFN-gamma mRNA in four patients. These results suggest that detection of IFN- gamma gene expression in pretreatment BMMC from aplastic patients using PCR may be helpful in predicting a good response to CyA therapy.

Intravenous administration of bone marrow mononuclear cells alleviates hearing loss after transient cochlear ischemia through paracrine effects

Neuroreport ◽  
2014 ◽  
Vol 25 (11) ◽  
pp. 807-813
Author(s):  
Taro Takagi ◽  
Tadashi Yoshida ◽  
Masahiro Okada ◽  
Ryuji Hata ◽  
Naohito Hato ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hearing Loss ◽  
Intravenous Administration ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Paracrine Effects

Research of Gene Expression in Patients with Myelodysplastic Syndromes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4433-4433
Author(s):  
Bao-An Chen ◽  
Bo Zhang ◽  
Chong Gao ◽  
Guo-Hua Xia ◽  
Ze-ye Shao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Clinical Significance ◽  
Myelodysplastic Syndromes ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Bone Marrow Mononuclear Cells ◽  
Rt Pcr ◽  
Normal People ◽  
Significant Difference

Abstract Abstract 4433 Object This study was aimed to investigate the expression of c-FLIPL, c-FLIPS and DLK1 mRNA in Myelodysplastic Syndromes (MDS) patients, as compared with normal people and AML patients, and to find its clinical significance. Methods The expression of c-FLIPL, c-FLIPS and DLK1 mRNA in bone marrow mononuclear cells (BMNNC) of 16 patients with MDS, 8 patients with AML and 3 controls were detected by RT-PCR. Results The expression of DLK1 mRNA was up-regulated in MDS, including RA and RAEB, as compared with controls(P<0.05). There was no significant difference in expression of DLK1 between RA and RAEB(P>0.05). The expression of DLK1 was significant higher in AML patients, compared with controls(P<0.05). There was no significant difference between MDS and AML patients(P>0.05). The expression of c-FLIPL mRNA was higher than that in controls, both in RA and RAEB(P<0.05). There was no significant difference in expression of c-FLIPL between RA and RAEB(P>0.05). In eight AML patients, c-FLIPL gene's expression was up-regulated, as compared with controls(P<0.05). Between AML and MDS patients, there was no significant difference(P>0.05); The expression of c-FLIPS mRNA had no significant difference between MDS patients and controls(P>0.05), but its expression in RAEB was significant higher as compared with RA patients and controls(P<0.05). And in AML patients, the expression of c-FLIPS was higher than that in controls(P<0.05), but there was no significant difference between AML and MDS patients(P>0.05). Conclusion It is concluded that the expressions of DLK1, c-FLIPL and c-FLIPS mRNA in MDS/AML patients are abnormal as compared with normal people, although there are no significant difference have been found between AML and MDS. These genes may play critical roles in escaping malignant clone of MDS from apoptosis and acquiring the ability to divide unlimitedly, they can become important indexes for evaluating of development in MDS. Disclosures: No relevant conflicts of interest to declare.

Identification of Gene Expression Based Prognostic Markers in the Hematopoietic Stem Cells of Patients with Myelodysplastic Syndromes

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3857-3857
Author(s):  
Andrea Pellagatti ◽  
Axel Benner ◽  
Ken I Mills ◽  
Mario Cazzola ◽  
Aristoteles Giagounidis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Principal Components ◽  
Myelodysplastic Syndromes ◽  
Expression Profiling ◽  
Mononuclear Cells ◽  
Patient Survival ◽  
Gene Signature ◽  
Bone Marrow Mononuclear Cells ◽  
Cd34 Cells

Abstract Abstract 3857 The diagnosis of patients with myelodysplastic syndromes (MDS) is largely dependent on morphologic examination of bone marrow aspirates. Several criteria that form the basis of the classifications and scoring systems most commonly used in clinical practice are affected by operator-dependent variation. In order to identify more standardized molecular markers that would allow a more reliable prediction of prognosis, we have used gene expression profiling (GEP) data on CD34+ cells from MDS patients to determine the relationship between gene expression levels and prognosis in this disorder. GEP data on CD34+ cells from 125 MDS patients with a minimum 12-month follow-up since date of bone marrow sample collection were included in this study. Prediction for overall survival was performed using supervised principal components (“SuperPC”) and lasso penalized Cox proportional hazards regression applying the “Coxnet” algorithm. Supervised principal components analysis was performed on patients randomly split in a training set (n=84) and a test set (n=41), and 139 genes were identified the expression of which was significantly associated with MDS patient survival, including LEF1, CDH1, WT1 and MN1. In order to identify a smaller set of genes associated with patient survival, a second approach aiming at building sparse prediction models was used. A model was generated using the Coxnet algorithm and a predictor consisting of 20 genes was identified. Eight genes identified by the supervised principal components method were in common with the genes identified by the Coxnet model: ADHFE1, BTBD6, CPT1B, LEF1, FRMD6, GPR114, C7orf58 and LOC100286844. The Coxnet predictor outperformed other predictors including one which additionally used clinical information. To validate our findings, we evaluated the performance of our prognostic Coxnet gene signature in an independent gene expression profiling dataset on MDS bone marrow mononuclear cells (Mills et al, Gene Expression Omnibus series GSE15061). Our Coxnet gene signature based on CD34+ cells significantly identified a low-risk patient group in this independent GEP dataset based on unsorted bone marrow mononuclear cells, demonstrating that our signature is robust and may be applicable to bone marrow cells without the need to isolate CD34+ cells. These GEP-based signatures correlating with clinical outcome may significantly contribute to a refined risk classification of MDS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2532-2535 ◽  
Author(s):  
S Nakao ◽  
M Yamaguchi ◽  
S Shiobara ◽  
T Yokoi ◽  
T Miyawaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Aplastic Anemia ◽  
Interferon Gamma ◽  
Messenger Rna ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Ifn Gamma ◽  
Exact Test ◽  
Transfusion Independence

Abstract Cyclosporine (CyA) therapy has been shown to be effective in some patients with aplastic anemia. In an attempt to characterize aplastic patients likely to benefit from CyA therapy, we examined bone marrow mononuclear cells (BMMC) obtained before therapy from 23 patients with aplastic anemia, who were treated with CyA alone. Expression of four myelosuppressive cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and interferon-gamma (IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1 alpha was readily detectable at variable levels in BMMC from normal and transfused controls as well as in BMMC from aplastic patients. In contrast, IFN-gamma mRNA was only demonstrable in BMMC from some patients with aplastic anemia, irrespective of a history of transfusions. Of 13 patients who responded to CyA therapy and achieved transfusion-independence, IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only detectable in 3 of 10 patients refractory to CyA therapy (P = .003, Fisher's exact test). Follow-up examination of BMMC obtained from seven CyA-responding patients after hematologic remission showed disappearance of IFN-gamma mRNA in four patients. These results suggest that detection of IFN- gamma gene expression in pretreatment BMMC from aplastic patients using PCR may be helpful in predicting a good response to CyA therapy.

Inhibition of Multiple Myeloma Cells Growth by AS602868, a Pharmacological Inhibitor of IKK2.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3472-3472 ◽  
Author(s):  
Michel Jourdan ◽  
Jerome Moreaux ◽  
Dirk Hose ◽  
Jean-Francois Rossi ◽  
Karène Mahtouk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Hematopoietic Stem ◽  
Myeloma Cells

Abstract The NF-κB pathway is involved in the physiological regulation of cell proliferation in many cell types as well as in the resistance of several malignancies to cell death. The pathophysiologic basis for multiple myeloma (MM) has been attributed to the dysregulation of various paracrine or autocrine growth factor loops and to perturbations in several signal transduction pathways including IKK/NF-κB. The aim of the present study was to investigate the effect of a pharmaceutical IKK2 inhibitor (IKK2-I), the anilinopyrimidine derivative AS602868 (Serono International SA), on the in vitro growth of human MM cell lines (HMCL) and primary MM cells. We evaluated the effect of AS602868 on the proliferation and the survival of 12 IL-6-dependent HCML and 2 autonomously growing HCML as well as on the survival of total bone marrow mononuclear cells from patients with newly diagnosed MM (n = 6) or with relapsing MM (n = 7). Results show that using HMCL or primary MM cells, AS602868 induces a clear dose-dependent inhibition of MM cell growth (the 50% inhibitory concentration (IC50) ranging from 0.28 to 8.3 μM, mean IC50 = 2.6 μM on HCML). It was shown using HMCL that the growth inhibition induced by AS602868 is the result of a simultaneous induction of apoptosis and inhibition of the cell cycle progression. Importantly, AS602868 does not alter the survival of other bone marrow mononuclear cells (CD138−) co-cultured with primary MM (CD138+) cells except on CD34+ hematopoietic stem cells. Interestingly, using gene expression profiling with Affymetrix microarrays on 13 HMCL, we show that the resistance (high IC50) to AS602868 inhibitor is strongly correlated to APRIL gene expression (r =.7603, p <.01). Thus, an autocrine production of APRIL confers a resistance to the AS602868 IKK2-I. This can be explained since APRIL has been shown to activate the alternative NF-κB pathway which implicates an IKK complex composed of IKK1 homodimers instead of the IKK1/IKK2/NEMO complex involved in the canonical NF-κB pathway. The results demonstrate the important role of NF-κB in maintaining survival of MM cells and suggest that a pharmacological inhibition of the NF-κB pathway by an IKK2-I, AS602868, can efficiently kill myeloma cell lines or primary myeloma cells and might represent an innovative approach for treating MM patients.

scholarly journals Evaluation of Tat-Encoding Bicistronic Human Immunodeficiency Virus Type 1 Gene Transfer Vectors in Primary Canine Bone Marrow Mononuclear Cells

2002 ◽  
Vol 76 (14) ◽  
pp. 7334-7342 ◽  
Author(s):  
Narasimhachar Srinivasakumar ◽  
Michail Zaboikin ◽  
Tatiana Zaboikina ◽  
Friedrich Schuening
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Gene Transfer ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Immunodeficiency Virus ◽  
Transfer Vectors ◽  
Hiv 1 ◽  
Primary Canine

ABSTRACT Tat-encoding human immunodeficiency virus type 1 (HIV-1) gene transfer vectors were evaluated in primary canine bone marrow mononuclear cells. Tat vectors provided higher levels of gene expression than vectors with internal promoters. The HIV-1 vector was also more efficient than Moloney murine leukemia virus (MoMLV) vectors for transduction of canine bone marrow mononuclear cells in vitro. Transplantation experiments in dogs with transduced autologous marrow cells confirmed the superiority of HIV-1 vectors over MoMLV vectors for gene transfer into canine bone marrow cells. Tat vectors may be useful not only for providing high levels of therapeutic gene expression in hematopoietic cells but also for study of the biological effects of Tat in those tissues in the canine model.

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