The Experts below are selected from a list of 11070 Experts worldwide ranked by ideXlab platform
Richard J Dandrea - One of the best experts on this subject based on the ideXlab platform.
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Hematopoietic Growth Factor mimetics from concept to clinic
Cytokine & Growth Factor Reviews, 2009Co-Authors: Michelle Perugini, Antiopi Varelias, Timothy Sadlon, Richard J DandreaAbstract:Hematopoietic Growth Factor (HGF) mimetics offer a number of attractive advantages as therapeutic agents. Small chemical compounds, in particular, provide reduced cost and oral availability. As many of these mimetics are unrelated in structure to the normal cytokine the immunogenic response is not a significant issue. Isolation of small peptide agonists for erythropoietin (EPO) and thrombopoietin (TPO) receptors has been associated with significant translational challenges and here we summarize approaches used to achieve the potency and stability required for clinical utility. We also compare and contrast the initial screening approaches, and the translational and clinical issues associated with two recently approved TPO mimetics, romiplostim and the orally available eltrombopag. Finally we summarize the development and clinical findings for the EPO mimetic, Hematide™, consider alternative approaches, and discuss the future potential for isolation of Growth Factor (GF) mimetics.
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bmp4 its role in development of the Hematopoietic system and potential as a Hematopoietic Growth Factor
Stem Cells, 2004Co-Authors: Timothy Sadlon, Ian D Lewis, Richard J DandreaAbstract:Blood formation occurs throughout the life of an individual in a process driven by Hematopoietic stem cells (HSCs). The ability of bone marrow (BM) and cord blood (CB) HSC to undergo self-renewal and develop into multiple blood lineages has made these cells an important clinical resource. Transplantation with BM- and CB-derived HSCs is now used extensively for treatment of hematological disorders, malignancies, and immunodeficiencies. An understanding of the embryonic origin of HSC and the Factors regulating their generation and expansion in vivo will provide important information for the manipulation of these cells ex vivo. This is critical for the further development of CB transplantation, the potential of which is limited by small numbers of HSC in the donor population. Although the origins of HSCs have become clearer and progress has been made in identifying genes that are critical for the formation and maintenance of HSCs, less is known about the signals that commit specific populations of mesodermal precursors to Hematopoietic cell fate. Critical signals acting on these precursor cells are likely to be derived from visceral endoderm in yolk sac and from underlying stroma in the aorta-gonad-mesonephros region. Here we summarize briefly the origin of yolk sac and embryonic HSCs before detailing evidence that bone morphogenic protein-4 (BMP4) has a crucial role in Xenopus and mammalian HSC development. We discuss evidence that BMP4 acts as a Hematopoietic Growth Factor and review its potential to modulate HSC in ex vivo expansion cultures from cord blood.
Linsheng Song - One of the best experts on this subject based on the ideXlab platform.
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a cytokine like Factor astakine accelerates the hemocyte production in pacific oyster crassostrea gigas
Developmental and Comparative Immunology, 2016Co-Authors: Shuai Jiang, Lusheng Xin, Lingling Wang, Hao Wang, Limei Qiu, Linsheng SongAbstract:Astakine has been reported to be a Hematopoietic Growth Factor of prokineticin homolog firstly found in arthropods freshwater crayfish Pacifastacus leniusculus. In the present study, an astakine homologous gene was identified from Pacific oyster Crassostrea gigas (designated CgAstakine). The full length cDNA of CgAstakine encoded a polypeptide of 103 amino acids containing a prokineticin (PK) domain homologous to that in astakine from freshwater crayfish P. leniusculus. The deduced amino acid sequence of CgAstakine shared higher similarity with those of other invertebrate astakines than prokineticins from vertebrates. The mRNA of CgAstakine was highly expressed in hepatopancreas and adductor muscle of oyster, while the CgAstakine protein was mainly distributed in hepatopancreas, gill and hemocytes. The mRNA expression of CgAstakine in hemocytes was significantly increased (p < 0.01) and maintained at a high level from 3 h to 9 h after Vibrio anguillarum challenge. After the oyster hemocytes were incubated with 5 μg/mL recombinant CgAstakine protein (rCgAstakine) for 24 h in vitro, the proliferation of hemocytes was significantly increased to 1.89 fold of that in control group (p < 0.05). Moreover, the total count of oyster hemocytes was significantly upregulated (2.45 fold of that in control group, p < 0.05) at 12 h after the oysters were received an injection of rCgAstakine (0.5 μg/g). These results collectively indicated that CgAstakine could modulate the hemocytes proliferation both in vitro and in vivo, and probably involved in the Hematopoietic process fighting against the invasion of foreign pathogens.
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a cytokine like Factor astakine accelerates the hemocyte production in pacific oyster crassostrea gigas
Developmental and Comparative Immunology, 2016Co-Authors: Yiqun Li, Shuai Jiang, Lingling Wang, Hao Wang, Meijia Li, Linsheng SongAbstract:Astakine has been reported to be a Hematopoietic Growth Factor of prokineticin homolog firstly found in arthropods freshwater crayfish Pacifastacus leniusculus. In the present study, an astakine homologous gene was identified from Pacific oyster Crassostrea gigas (designated CgAstakine). The full length cDNA of CgAstakine encoded a polypeptide of 103 amino acids containing a prokineticin (PK) domain homologous to that in astakine from freshwater crayfish P. leniusculus. The deduced amino acid sequence of CgAstakine shared higher similarity with those of other invertebrate astakines than prokineticins from vertebrates. The mRNA of CgAstakine was highly expressed in hepatopancreas and adductor muscle of oyster, while the CgAstakine protein was mainly distributed in hepatopancreas, gill and hemocytes. The mRNA expression of CgAstaldne in hemocytes was significantly increased (p < 0.01) and maintained at a high level from 3 h to 9 h after Vibrio anguillarum challenge. After the oyster hemocytes were incubated with 5 mu g/mL recombinant CgAstakine protein (rCgAstakine) for 24 h in vitro, the proliferation of hemocytes was significantly increased to 1.89 fold of that in control group (p < 0.05). Moreover, the total count of oyster hemocytes was significantly upregulated (2.45 fold of that in control group, p < 0.05) at 12 h after the oysters were received an injection of rCgAstakine (0.5 mu g/g). These results collectively indicated that CgAstakine could modulate the hemocytes proliferation both in vitro and in vivo, and probably involved in the Hematopoietic process fighting against the invasion of foreign pathogens. (C) 2015 Elsevier Ltd. All rights reserved.
Flora Zavala - One of the best experts on this subject based on the ideXlab platform.
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treatment with granulocyte colony stimulating Factor prevents diabetes in nod mice by recruiting plasmacytoid dendritic cells and functional cd4 cd25 regulatory t cells
Diabetes, 2005Co-Authors: Hassen Kared, Annie Masson, Homa Adlebiassette, Jeanfrancois Bach, Lucienne Chatenoud, Flora ZavalaAbstract:Accumulating evidence that granulocyte colony−stimulating Factor (G-CSF), the key Hematopoietic Growth Factor of the myeloid lineage, not only represents a major component of the endogenous response to infections, but also affects adaptive immune responses, prompted us to investigate the therapeutic potential of G-CSF in autoimmune type 1 diabetes. Treatment with G-CSF protected NOD mice from developing spontaneous diabetes. G-CSF triggered marked recruitment of dendritic cells (DCs), particularly immature CD11cloB220+ plasmacytoid DCs, with reduced costimulatory signal expression and higher interferon-α but lower interleukin-12p70 release capacity than DCs in excipient-treated mice. G-CSF recipients further displayed accumulation of functional CD4+CD25+ regulatory T-cells that produce transforming Growth Factor-β1 (TGF-β1) and actively suppressed diabetes transfer by diabetogenic effector cells in secondary NOD-SCID recipients. G-CSF’s ability to promote key tolerogenic interactions between DCs and regulatory T-cells was demonstrated by enhanced recruitment of TGF-β1−expressing CD4+CD25+ cells after adoptive transfer of DCs isolated from G-CSF− relative to vehicle-treated mice into naive NOD recipients. The present results suggest that G-CSF, a promoter of tolerogenic DCs, may be evaluated for the treatment of human type 1 diabetes, possibly in association with direct inhibitors of T-cell activation. They also provide a rationale for a protective role of the endogenous G-CSF produced during infections in early diabetes.
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treatment with granulocyte colony stimulating Factor prevents diabetes in nod mice by recruiting plasmacytoid dendritic cells and functional cd4 cd25 regulatory t cells
Diabetes, 2005Co-Authors: Hassen Kared, Annie Masson, Homa Adlebiassette, Jeanfrancois Bach, Lucienne Chatenoud, Flora ZavalaAbstract:Accumulating evidence that granulocyte colony-stimulating Factor (G-CSF), the key Hematopoietic Growth Factor of the myeloid lineage, not only represents a major component of the endogenous response to infections, but also affects adaptive immune responses, prompted us to investigate the therapeutic potential of G-CSF in autoimmune type 1 diabetes. Treatment with G-CSF protected NOD mice from developing spontaneous diabetes. G-CSF triggered marked recruitment of dendritic cells (DCs), particularly immature CD11c(lo)B220(+) plasmacytoid DCs, with reduced costimulatory signal expression and higher interferon-alpha but lower interleukin-12p70 release capacity than DCs in excipient-treated mice. G-CSF recipients further displayed accumulation of functional CD4(+)CD25(+) regulatory T-cells that produce transforming Growth Factor-beta1 (TGF-beta1) and actively suppressed diabetes transfer by diabetogenic effector cells in secondary NOD-SCID recipients. G-CSF's ability to promote key tolerogenic interactions between DCs and regulatory T-cells was demonstrated by enhanced recruitment of TGF-beta1-expressing CD4(+)CD25(+) cells after adoptive transfer of DCs isolated from G-CSF- relative to vehicle-treated mice into naive NOD recipients. The present results suggest that G-CSF, a promoter of tolerogenic DCs, may be evaluated for the treatment of human type 1 diabetes, possibly in association with direct inhibitors of T-cell activation. They also provide a rationale for a protective role of the endogenous G-CSF produced during infections in early diabetes.
Andre Herbelin - One of the best experts on this subject based on the ideXlab platform.
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il 33 activates unprimed murine basophils directly in vitro and induces their in vivo expansion indirectly by promoting Hematopoietic Growth Factor production
Journal of Immunology, 2009Co-Authors: Elke Schneider, Annefrance Petitbertron, Rachel Bricard, Melanie Levasseur, Abdelrauf Ramadan, J Girard, Andre HerbelinAbstract:IL-33, a new member of the IL-1 family, has been described as an important inducer of Th2 cytokines and mediator of inflammatory responses. In this study, we demonstrate that murine basophils sorted directly from the bone marrow, without prior exposure to IL-3 or Fc(epsilon)R cross-linking, respond to IL-33 alone by producing substantial amounts of histamine, IL-4, and IL-6. These cells express ST2 constitutively and generate a cytokine profile that differs from their IL-3-induced counterpart by a preferential production of IL-6. In vivo, IL-33 promotes basophil expansion in the bone marrow (BM) through an indirect mechanism of action depending on signaling through the beta(c) chain shared by receptors for IL-3, GM-CSF, and IL-5. IL-3 can still signal through its specific beta(IL-3) chain in these mutant mice, which implies that it is not the unique Growth-promoting mediator in this setup, but requires IL-5 and/or GMCSF. Our results support a major role of the latter Growth Factor, which is readily generated by total BM cells as well as sorted basophils in response to IL-33 along with low amounts of IL-3. Furthermore, GM-CSF amplifies IL-3-induced differentiation of basophils from BM cells, whereas IL-5 that is also generated in vivo, affects neither their functions nor their Growth in vitro or in vivo. In conclusion, our data provide the first evidence that IL-33 not only activates unprimed basophils directly, but also promotes their expansion in vivo through induction of GM-CSF and IL-3.
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il 33 activates unprimed murine basophils directly in vitro and induces their in vivo expansion indirectly by promoting Hematopoietic Growth Factor production
Journal of Immunology, 2009Co-Authors: Elke Schneider, Annefrance Petitbertron, Rachel Bricard, Melanie Levasseur, Abdelrauf Ramadan, J Girard, Andre Herbelin, Michel DyAbstract:IL-33, a new member of the IL-1 family, has been described as an important inducer of Th2 cytokines and mediator of inflammatory responses. In this study, we demonstrate that murine basophils sorted directly from the bone marrow, without prior exposure to IL-3 or FceR cross-linking, respond to IL-33 alone by producing substantial amounts of histamine, IL-4, and IL-6. These cells express ST2 constitutively and generate a cytokine profile that differs from their IL-3-induced counterpart by a preferential production of IL-6. In vivo, IL-33 promotes basophil expansion in the bone marrow (BM) through an indirect mechanism of action depending on signaling through the β c chain shared by receptors for IL-3, GM-CSF, and IL-5. IL-3 can still signal through its specific β IL-3 chain in these mutant mice, which implies that it is not the unique Growth-promoting mediator in this setup, but requires IL-5 and/or GMCSF. Our results support a major role of the latter Growth Factor, which is readily generated by total BM cells as well as sorted basophils in response to IL-33 along with low amounts of IL-3. Furthermore, GM-CSF amplifies IL-3-induced differentiation of basophils from BM cells, whereas IL-5 that is also generated in vivo, affects neither their functions nor their Growth in vitro or in vivo. In conclusion, our data provide the first evidence that IL-33 not only activates unprimed basophils directly, but also promotes their expansion in vivo through induction of GM-CSF and IL-3.
Elke Schneider - One of the best experts on this subject based on the ideXlab platform.
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il 33 activates unprimed murine basophils directly in vitro and induces their in vivo expansion indirectly by promoting Hematopoietic Growth Factor production
Journal of Immunology, 2009Co-Authors: Elke Schneider, Annefrance Petitbertron, Rachel Bricard, Melanie Levasseur, Abdelrauf Ramadan, J Girard, Andre HerbelinAbstract:IL-33, a new member of the IL-1 family, has been described as an important inducer of Th2 cytokines and mediator of inflammatory responses. In this study, we demonstrate that murine basophils sorted directly from the bone marrow, without prior exposure to IL-3 or Fc(epsilon)R cross-linking, respond to IL-33 alone by producing substantial amounts of histamine, IL-4, and IL-6. These cells express ST2 constitutively and generate a cytokine profile that differs from their IL-3-induced counterpart by a preferential production of IL-6. In vivo, IL-33 promotes basophil expansion in the bone marrow (BM) through an indirect mechanism of action depending on signaling through the beta(c) chain shared by receptors for IL-3, GM-CSF, and IL-5. IL-3 can still signal through its specific beta(IL-3) chain in these mutant mice, which implies that it is not the unique Growth-promoting mediator in this setup, but requires IL-5 and/or GMCSF. Our results support a major role of the latter Growth Factor, which is readily generated by total BM cells as well as sorted basophils in response to IL-33 along with low amounts of IL-3. Furthermore, GM-CSF amplifies IL-3-induced differentiation of basophils from BM cells, whereas IL-5 that is also generated in vivo, affects neither their functions nor their Growth in vitro or in vivo. In conclusion, our data provide the first evidence that IL-33 not only activates unprimed basophils directly, but also promotes their expansion in vivo through induction of GM-CSF and IL-3.
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il 33 activates unprimed murine basophils directly in vitro and induces their in vivo expansion indirectly by promoting Hematopoietic Growth Factor production
Journal of Immunology, 2009Co-Authors: Elke Schneider, Annefrance Petitbertron, Rachel Bricard, Melanie Levasseur, Abdelrauf Ramadan, J Girard, Andre Herbelin, Michel DyAbstract:IL-33, a new member of the IL-1 family, has been described as an important inducer of Th2 cytokines and mediator of inflammatory responses. In this study, we demonstrate that murine basophils sorted directly from the bone marrow, without prior exposure to IL-3 or FceR cross-linking, respond to IL-33 alone by producing substantial amounts of histamine, IL-4, and IL-6. These cells express ST2 constitutively and generate a cytokine profile that differs from their IL-3-induced counterpart by a preferential production of IL-6. In vivo, IL-33 promotes basophil expansion in the bone marrow (BM) through an indirect mechanism of action depending on signaling through the β c chain shared by receptors for IL-3, GM-CSF, and IL-5. IL-3 can still signal through its specific β IL-3 chain in these mutant mice, which implies that it is not the unique Growth-promoting mediator in this setup, but requires IL-5 and/or GMCSF. Our results support a major role of the latter Growth Factor, which is readily generated by total BM cells as well as sorted basophils in response to IL-33 along with low amounts of IL-3. Furthermore, GM-CSF amplifies IL-3-induced differentiation of basophils from BM cells, whereas IL-5 that is also generated in vivo, affects neither their functions nor their Growth in vitro or in vivo. In conclusion, our data provide the first evidence that IL-33 not only activates unprimed basophils directly, but also promotes their expansion in vivo through induction of GM-CSF and IL-3.