The Experts below are selected from a list of 462 Experts worldwide ranked by ideXlab platform
Heinrich Sauer - One of the best experts on this subject based on the ideXlab platform.
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The milk thistle (Silybum marianum) compound Silibinin stimulates Leukopoiesis from mouse embryonic stem cells.
Phytotherapy research : PTR, 2018Co-Authors: Fatemeh Sharifpanah, Maria Wartenberg, Enas Hussein Ali, Heinrich SauerAbstract:The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis and Leukopoiesis are interrelated, the effect of Silibinin on Leukopoiesis of ES cells was investigated. Treatment of differentiating ES cells with hydrosoluble Silibinin-C-2',3-dihydrogen succinate dose-dependent increased the number of CD18+ , CD45+ , and CD68+ cells, indicating leukocyte/macrophage differentiation. Silibinin treatment activated phosphoinositide 3-kinase (PI3K), AKT (protein kinase B), signal transducer and activator of transcription 3 (STAT3), stimulated hypoxia-induced factor-1α (HIF-1α), and vascular endothelial growth factor receptor 2 (VEGFR2) expression and raised intracellular nitric oxide (NO). Western blot experiments showed that upon coincubation with either the PI3K inhibitor LY294002, the STAT3 inhibitor Stattic, the AKT antagonist AKT inhibitor VIII, or the NO inhibitor L-NAME, the Silibinin-induced expression of CD18, CD45, and CD68 was abolished. Moreover, the stimulation of HIF-1α and VEGFR2 expression was blunted upon STAT3 and PI3K/AKT inhibition. Treatment of differentiating ES cells with L-NAME abolished the stimulation of VEGFR2 and VE-cadherin expression achieved with Silibinin, indicating that NO is involved in vasculogenesis and leukocyte differentiation pathways. In summary, the data of the present study demonstrate that Silibinin stimulates leukocyte differentiation of ES cells, which is associated to vasculogenesis and regulated by PI3K/AKT-, STAT3-, and NO-mediated signaling.
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Stimulation of vasculogenesis and Leukopoiesis of embryonic stem cells by extracellular transfer RNA and ribosomal RNA.
Free radical biology & medicine, 2015Co-Authors: Fatemeh Sharifpanah, Sepali De Silva, Mohamed M. Bekhite, Jorge Hurtado-oliveros, Klaus T. Preissner, Maria Wartenberg, Heinrich SauerAbstract:Abstract Objective Cell injury releases nucleic acids supporting inflammation and stem cell activation. Here, the impact of extracellular ribonucleic acid, especially transfer RNA (ex-tRNA), on vasculogenesis and Leukopoiesis of mouse embryonic stem (ES) cells was investigated. Approach and results ex-tRNA, whole cell RNA and ribosomal RNA (ex-rRNA) but not DNA increased CD31-positive vascular structures in embryoid bodies. Ex-tRNA and ex-rRNA increased numbers of VEGFR2+, CD31+ and VE-cadherin+ vascular cells as well as CD18+, CD45+ and CD68+ cells, indicating leukocyte/macrophage differentiation. This was paralleled by mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-165 (VEGF165) and neuropilin 1 (NRP1), phosphorylation of phosphatidyl inositol 3-kinase (PI3K) and VEGF receptor 2 (VEGFR2) as well as mRNA expression of α-smooth muscle actin (α-SMA). ex-tRNA was taken up by endosomes, increased expression of the pro-angiogenic semaphorin B4 receptor plexin B1 as well as the ephrin-type B receptor 4 (EphB4) and ephrinB2 ligand and enhanced cell migration, which was inhibited by the VEGFR2 antagonist SU5614 and the PI3K inhibitor LY294002. This likewise abolished the effects of ex-tRNA on vasculogenesis and Leukopoiesis of ES cells. Ex-tRNA increased NOX1, NOX2, NOX4 and DUOX2 mRNA and boosted the generation of superoxide and hydrogen peroxide which was inhibited by radical scavengers, the NADPH oxidase inhibitors apocynin, VAS2870, ML171, and plumbagin as well as shRNA silencing of NOX1 and NOX4. Conclusions Our findings indicate that ex-tRNA treatment induces vasculogenesis and Leukopoiesis of ES cells via superoxide/hydrogen peroxide generated by NADPH oxidase and activation of VEGFR2 and PI3K.
Fatemeh Sharifpanah - One of the best experts on this subject based on the ideXlab platform.
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The milk thistle (Silybum marianum) compound Silibinin stimulates Leukopoiesis from mouse embryonic stem cells.
Phytotherapy research : PTR, 2018Co-Authors: Fatemeh Sharifpanah, Maria Wartenberg, Enas Hussein Ali, Heinrich SauerAbstract:The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis and Leukopoiesis are interrelated, the effect of Silibinin on Leukopoiesis of ES cells was investigated. Treatment of differentiating ES cells with hydrosoluble Silibinin-C-2',3-dihydrogen succinate dose-dependent increased the number of CD18+ , CD45+ , and CD68+ cells, indicating leukocyte/macrophage differentiation. Silibinin treatment activated phosphoinositide 3-kinase (PI3K), AKT (protein kinase B), signal transducer and activator of transcription 3 (STAT3), stimulated hypoxia-induced factor-1α (HIF-1α), and vascular endothelial growth factor receptor 2 (VEGFR2) expression and raised intracellular nitric oxide (NO). Western blot experiments showed that upon coincubation with either the PI3K inhibitor LY294002, the STAT3 inhibitor Stattic, the AKT antagonist AKT inhibitor VIII, or the NO inhibitor L-NAME, the Silibinin-induced expression of CD18, CD45, and CD68 was abolished. Moreover, the stimulation of HIF-1α and VEGFR2 expression was blunted upon STAT3 and PI3K/AKT inhibition. Treatment of differentiating ES cells with L-NAME abolished the stimulation of VEGFR2 and VE-cadherin expression achieved with Silibinin, indicating that NO is involved in vasculogenesis and leukocyte differentiation pathways. In summary, the data of the present study demonstrate that Silibinin stimulates leukocyte differentiation of ES cells, which is associated to vasculogenesis and regulated by PI3K/AKT-, STAT3-, and NO-mediated signaling.
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Stimulation of vasculogenesis and Leukopoiesis of embryonic stem cells by extracellular transfer RNA and ribosomal RNA.
Free radical biology & medicine, 2015Co-Authors: Fatemeh Sharifpanah, Sepali De Silva, Mohamed M. Bekhite, Jorge Hurtado-oliveros, Klaus T. Preissner, Maria Wartenberg, Heinrich SauerAbstract:Abstract Objective Cell injury releases nucleic acids supporting inflammation and stem cell activation. Here, the impact of extracellular ribonucleic acid, especially transfer RNA (ex-tRNA), on vasculogenesis and Leukopoiesis of mouse embryonic stem (ES) cells was investigated. Approach and results ex-tRNA, whole cell RNA and ribosomal RNA (ex-rRNA) but not DNA increased CD31-positive vascular structures in embryoid bodies. Ex-tRNA and ex-rRNA increased numbers of VEGFR2+, CD31+ and VE-cadherin+ vascular cells as well as CD18+, CD45+ and CD68+ cells, indicating leukocyte/macrophage differentiation. This was paralleled by mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-165 (VEGF165) and neuropilin 1 (NRP1), phosphorylation of phosphatidyl inositol 3-kinase (PI3K) and VEGF receptor 2 (VEGFR2) as well as mRNA expression of α-smooth muscle actin (α-SMA). ex-tRNA was taken up by endosomes, increased expression of the pro-angiogenic semaphorin B4 receptor plexin B1 as well as the ephrin-type B receptor 4 (EphB4) and ephrinB2 ligand and enhanced cell migration, which was inhibited by the VEGFR2 antagonist SU5614 and the PI3K inhibitor LY294002. This likewise abolished the effects of ex-tRNA on vasculogenesis and Leukopoiesis of ES cells. Ex-tRNA increased NOX1, NOX2, NOX4 and DUOX2 mRNA and boosted the generation of superoxide and hydrogen peroxide which was inhibited by radical scavengers, the NADPH oxidase inhibitors apocynin, VAS2870, ML171, and plumbagin as well as shRNA silencing of NOX1 and NOX4. Conclusions Our findings indicate that ex-tRNA treatment induces vasculogenesis and Leukopoiesis of ES cells via superoxide/hydrogen peroxide generated by NADPH oxidase and activation of VEGFR2 and PI3K.
Ann E. Rundell - One of the best experts on this subject based on the ideXlab platform.
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An Integrative multi-lineage model of variation in Leukopoiesis and acute myelogenous leukemia
BMC Systems Biology, 2017Co-Authors: Joyatee M. Sarker, Serena M. Pearce, Robert P. Nelson, Tamara L. Kinzer-ursem, David M. Umulis, Ann E. RundellAbstract:Background Acute myelogenous leukemia (AML) progresses uniquely in each patient. However, patients are typically treated with the same types of chemotherapy, despite biological differences that lead to differential responses to treatment. Results Here we present a multi-lineage multi-compartment model of the hematopoietic system that captures patient-to-patient variation in both the concentration and rates of change of hematopoietic cell populations. By constraining the model against clinical hematopoietic cell recovery data derived from patients who have received induction chemotherapy, we identified trends for parameters that must be met by the model; for example, the mitosis rates and the probability of self-renewal of progenitor cells are inversely related. Within the data-consistent models, we found 22,796 parameter sets that meet chemotherapy response criteria. Simulations of these parameter sets display diverse dynamics in the cell populations. To identify large trends in these model outputs, we clustered the simulated cell population dynamics using k-means clustering and identified thirteen ‘representative patient’ dynamics. In each of these patient clusters, we simulated AML and found that clusters with the greatest mitotic capacity experience clinical cancer outcomes more likely to lead to shorter survival times. Conversely, other parameters, including lower death rates or mobilization rates, did not correlate with survival times. Conclusions Using the multi-lineage model of hematopoiesis, we have identified several key features that determine leukocyte homeostasis, including self-renewal probabilities and mitosis rates, but not mobilization rates. Other influential parameters that regulate AML model behavior are responses to cytokines/growth factors produced in peripheral blood that target the probability of self-renewal of neutrophil progenitors. Finally, our model predicts that the mitosis rate of cancer is the most predictive parameter for survival time, followed closely by parameters that affect the self-renewal of cancer stem cells; most current therapies target mitosis rate, but based on our results, we propose that additional therapeutic targeting of self-renewal of cancer stem cells will lead to even higher survival rates.
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An Integrative multi-lineage model of variation in Leukopoiesis and acute myelogenous leukemia
BMC systems biology, 2017Co-Authors: Joyatee M. Sarker, Serena M. Pearce, Robert P. Nelson, Tamara L. Kinzer-ursem, David M. Umulis, Ann E. RundellAbstract:Acute myelogenous leukemia (AML) progresses uniquely in each patient. However, patients are typically treated with the same types of chemotherapy, despite biological differences that lead to differential responses to treatment. Here we present a multi-lineage multi-compartment model of the hematopoietic system that captures patient-to-patient variation in both the concentration and rates of change of hematopoietic cell populations. By constraining the model against clinical hematopoietic cell recovery data derived from patients who have received induction chemotherapy, we identified trends for parameters that must be met by the model; for example, the mitosis rates and the probability of self-renewal of progenitor cells are inversely related. Within the data-consistent models, we found 22,796 parameter sets that meet chemotherapy response criteria. Simulations of these parameter sets display diverse dynamics in the cell populations. To identify large trends in these model outputs, we clustered the simulated cell population dynamics using k-means clustering and identified thirteen ‘representative patient’ dynamics. In each of these patient clusters, we simulated AML and found that clusters with the greatest mitotic capacity experience clinical cancer outcomes more likely to lead to shorter survival times. Conversely, other parameters, including lower death rates or mobilization rates, did not correlate with survival times. Using the multi-lineage model of hematopoiesis, we have identified several key features that determine leukocyte homeostasis, including self-renewal probabilities and mitosis rates, but not mobilization rates. Other influential parameters that regulate AML model behavior are responses to cytokines/growth factors produced in peripheral blood that target the probability of self-renewal of neutrophil progenitors. Finally, our model predicts that the mitosis rate of cancer is the most predictive parameter for survival time, followed closely by parameters that affect the self-renewal of cancer stem cells; most current therapies target mitosis rate, but based on our results, we propose that additional therapeutic targeting of self-renewal of cancer stem cells will lead to even higher survival rates.
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Glossary of state variables and parameters for Leukopoiesis model.
2014Co-Authors: Devaraj Jayachandran, Ann E. Rundell, Robert E. Hannemann, Terry A. Vik, Doraiswami RamkrishnaAbstract:Glossary of state variables and parameters for Leukopoiesis model.
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Patient-specific parameters estimated for 6-MP, Leukopoiesis and MCV models.
2014Co-Authors: Devaraj Jayachandran, Ann E. Rundell, Robert E. Hannemann, Terry A. Vik, Doraiswami RamkrishnaAbstract:Patient-specific parameters estimated for 6-MP, Leukopoiesis and MCV models.
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Simplified schematics of the Leukopoiesis and erythropoiesis model.
2014Co-Authors: Devaraj Jayachandran, Ann E. Rundell, Robert E. Hannemann, Terry A. Vik, Doraiswami RamkrishnaAbstract:Stem cells reside in the bone marrow, proliferate, mature and enter the circulation as fully functional leukocytes. Stem cells receive biochemical feedback for proliferation from the circulating blood. On treatment initiation, 6-MP enters the bone marrow and imparts cytotoxicity to the stem cells. Leukocytes and RBC MCV in the circulating blood are routinely measured and used as a dose-limiting parameter. A. Leukopoiesis, B. Erythropoiesis. Additional compartment for MCV was added to account for the dynamic changes following 6-MP treatment. Solid arrows represent cellular movement; dashed arrow represents property changes.
Maria Wartenberg - One of the best experts on this subject based on the ideXlab platform.
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The milk thistle (Silybum marianum) compound Silibinin stimulates Leukopoiesis from mouse embryonic stem cells.
Phytotherapy research : PTR, 2018Co-Authors: Fatemeh Sharifpanah, Maria Wartenberg, Enas Hussein Ali, Heinrich SauerAbstract:The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis and Leukopoiesis are interrelated, the effect of Silibinin on Leukopoiesis of ES cells was investigated. Treatment of differentiating ES cells with hydrosoluble Silibinin-C-2',3-dihydrogen succinate dose-dependent increased the number of CD18+ , CD45+ , and CD68+ cells, indicating leukocyte/macrophage differentiation. Silibinin treatment activated phosphoinositide 3-kinase (PI3K), AKT (protein kinase B), signal transducer and activator of transcription 3 (STAT3), stimulated hypoxia-induced factor-1α (HIF-1α), and vascular endothelial growth factor receptor 2 (VEGFR2) expression and raised intracellular nitric oxide (NO). Western blot experiments showed that upon coincubation with either the PI3K inhibitor LY294002, the STAT3 inhibitor Stattic, the AKT antagonist AKT inhibitor VIII, or the NO inhibitor L-NAME, the Silibinin-induced expression of CD18, CD45, and CD68 was abolished. Moreover, the stimulation of HIF-1α and VEGFR2 expression was blunted upon STAT3 and PI3K/AKT inhibition. Treatment of differentiating ES cells with L-NAME abolished the stimulation of VEGFR2 and VE-cadherin expression achieved with Silibinin, indicating that NO is involved in vasculogenesis and leukocyte differentiation pathways. In summary, the data of the present study demonstrate that Silibinin stimulates leukocyte differentiation of ES cells, which is associated to vasculogenesis and regulated by PI3K/AKT-, STAT3-, and NO-mediated signaling.
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Stimulation of vasculogenesis and Leukopoiesis of embryonic stem cells by extracellular transfer RNA and ribosomal RNA.
Free radical biology & medicine, 2015Co-Authors: Fatemeh Sharifpanah, Sepali De Silva, Mohamed M. Bekhite, Jorge Hurtado-oliveros, Klaus T. Preissner, Maria Wartenberg, Heinrich SauerAbstract:Abstract Objective Cell injury releases nucleic acids supporting inflammation and stem cell activation. Here, the impact of extracellular ribonucleic acid, especially transfer RNA (ex-tRNA), on vasculogenesis and Leukopoiesis of mouse embryonic stem (ES) cells was investigated. Approach and results ex-tRNA, whole cell RNA and ribosomal RNA (ex-rRNA) but not DNA increased CD31-positive vascular structures in embryoid bodies. Ex-tRNA and ex-rRNA increased numbers of VEGFR2+, CD31+ and VE-cadherin+ vascular cells as well as CD18+, CD45+ and CD68+ cells, indicating leukocyte/macrophage differentiation. This was paralleled by mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-165 (VEGF165) and neuropilin 1 (NRP1), phosphorylation of phosphatidyl inositol 3-kinase (PI3K) and VEGF receptor 2 (VEGFR2) as well as mRNA expression of α-smooth muscle actin (α-SMA). ex-tRNA was taken up by endosomes, increased expression of the pro-angiogenic semaphorin B4 receptor plexin B1 as well as the ephrin-type B receptor 4 (EphB4) and ephrinB2 ligand and enhanced cell migration, which was inhibited by the VEGFR2 antagonist SU5614 and the PI3K inhibitor LY294002. This likewise abolished the effects of ex-tRNA on vasculogenesis and Leukopoiesis of ES cells. Ex-tRNA increased NOX1, NOX2, NOX4 and DUOX2 mRNA and boosted the generation of superoxide and hydrogen peroxide which was inhibited by radical scavengers, the NADPH oxidase inhibitors apocynin, VAS2870, ML171, and plumbagin as well as shRNA silencing of NOX1 and NOX4. Conclusions Our findings indicate that ex-tRNA treatment induces vasculogenesis and Leukopoiesis of ES cells via superoxide/hydrogen peroxide generated by NADPH oxidase and activation of VEGFR2 and PI3K.
Norbert E. Kaminski - One of the best experts on this subject based on the ideXlab platform.
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The challenges ahead in immunotoxicity assessment: An in vitro model of human Leukopoiesis
Current Opinion in Toxicology, 2017Co-Authors: Michael P. Holsapple, Anthony Bach, Lance K. Blevins, Robert Crawford, Norbert E. KaminskiAbstract:Abstract The science behind immunotoxicology continues to evolve. The goals of this paper are to highlight some of the challenges in immunotoxicity assessment that still need to be addressed. In a general sense, one of the challenges is the ability to translate results to humans. With the exception of pharmaceuticals, it is difficult to conduct studies in humans. As such, a number of in vitro models have been developed, and have been successfully applied to explore the effects of xenobiotics on human cells. In a more specific sense, this paper describes advances in a component of the human immune system that has, heretofore, been understudied – human Leukopoiesis.