The Experts below are selected from a list of 90 Experts worldwide ranked by ideXlab platform
Nihal Engin Vrana - One of the best experts on this subject based on the ideXlab platform.
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incorporation of resident macrophages in engineered tissues Multiple Cell Type response to microenvironment controlled macrophage laden gelatine hydrogels
Journal of Tissue Engineering and Regenerative Medicine, 2018Co-Authors: Camille Dollinger, Sait Ciftci, Helena Knopfmarques, Rabia Guner, Amir M Ghaemmaghami, Christian Debry, Julien Barthes, Nihal Engin VranaAbstract:The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key Cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, an in-vitro model of interaction was developed between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming Cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, naive THP-1 monocytes, endothelial Cells and fibroblasts were seeded on the gels as incoming Cells. The interaction was first monitored in the absence of the gels. To mimic resident macrophages, THP-1 Cells were encapsulated in the presence or absence of IL-4 to control their phenoType and then these hydrogels were seeded with incoming Cells. Without encapsulation, activated macrophages induce apoptosis in endothelial Cells. Once encapsulated no adverse effects were seen. Macrophage-laden hydrogels attracted more endothelial Cells and fibroblasts compared to monocytes-laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted Cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in more secretion of both pro- and anti-inflammatory cytokines compared to M2 stimulation. It was demonstrated that there is a distinct effect of encapsulated macrophages on the behaviour of the incoming Cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation.
Camille Dollinger - One of the best experts on this subject based on the ideXlab platform.
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incorporation of resident macrophages in engineered tissues Multiple Cell Type response to microenvironment controlled macrophage laden gelatine hydrogels
Journal of Tissue Engineering and Regenerative Medicine, 2018Co-Authors: Camille Dollinger, Sait Ciftci, Helena Knopfmarques, Rabia Guner, Amir M Ghaemmaghami, Christian Debry, Julien Barthes, Nihal Engin VranaAbstract:The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key Cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, an in-vitro model of interaction was developed between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming Cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, naive THP-1 monocytes, endothelial Cells and fibroblasts were seeded on the gels as incoming Cells. The interaction was first monitored in the absence of the gels. To mimic resident macrophages, THP-1 Cells were encapsulated in the presence or absence of IL-4 to control their phenoType and then these hydrogels were seeded with incoming Cells. Without encapsulation, activated macrophages induce apoptosis in endothelial Cells. Once encapsulated no adverse effects were seen. Macrophage-laden hydrogels attracted more endothelial Cells and fibroblasts compared to monocytes-laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted Cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in more secretion of both pro- and anti-inflammatory cytokines compared to M2 stimulation. It was demonstrated that there is a distinct effect of encapsulated macrophages on the behaviour of the incoming Cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation.
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Table_1_Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation.docx
2018Co-Authors: Julien Barthes, Camille Dollinger, Celine B. Muller, Urmas Liivas, Agnes Dupret-bories, Helena Knopf-marques, Nihal E. VranaAbstract:The function of soft tissues is intricately linked to their connections with the other systems of the body such as circulation, nervous system, and immune system. The presence of resident macrophages in tissues provides a means to control tissue homeostasis and also a way to react to the physical/biological insults and tissue damage. Thus, incorporation of resident macrophage like phenoType-controlled macrophages in engineered tissues can improve their fidelity as model tissues and also improve their rate of integration and facilitate the resolution of inflammation for regenerative medicine applications. Herein, we demonstrate two potential ways to immunoassist the remodeling process of engineered soft tissues in three-dimensional (3-D) gelatin based hydrogels containing fibroblasts and/or endothelial Cells: (i) with supplementation of interleukin-4 (IL-4) in the presence of macrophages and (ii) in tri-culture via naive monocytes or differentiated macrophages. The presence of IL-4 had a proliferative effect on fibroblasts, with a significant boosting effect on proliferation and cytokine secretion in the presence of differentiated macrophages with an upregulation of activin, interleukin-1 receptor antagonist (IL-1RA), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β), creating a more stimulating microenvironment. The addition of IL-4 in endothelial Cell/macrophage co-culture configuration improved the organization of the sprout-like structures, with a boost in proliferation at day 1 and with an upregulation of IL-6 and IL-1RA at the earliest stage in the presence of differentiated macrophages creating a favorable microenvironment for angiogenesis. In tri-culture conditions, the presence of monocytes or macrophages resulted in a denser tissue-like structure with highly remodeled hydrogels. The presence of differentiated macrophages had a boosting effect on the angiogenic secretory microenvironment, such as IL-6 and IL-8, without any additional cytokine supplementation. The presence of fibroblasts in combination with endothelial Cells also had a significant effect on the secretion of angiopoietin. Our results demonstrate that incorporation of macrophages in a resident macrophage function and their phenoType control have significant effects on the maturation and cytokine microenvironment of 3-D Multiple Cell Type-laden hydrogels, which can be harnessed for better integration of implantable systems and for more physiologically relevant in vitro tissue models with an immune component.
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Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation
Frontiers Media S.A., 2018Co-Authors: Camille Dollinger, Julien Barthes, Celine B. Muller, Urmas Liivas, Agnes Dupret-bories, Helena Knopf-marques, Nihal E. VranaAbstract:The function of soft tissues is intricately linked to their connections with the other systems of the body such as circulation, nervous system, and immune system. The presence of resident macrophages in tissues provides a means to control tissue homeostasis and also a way to react to the physical/biological insults and tissue damage. Thus, incorporation of resident macrophage like phenoType-controlled macrophages in engineered tissues can improve their fidelity as model tissues and also improve their rate of integration and facilitate the resolution of inflammation for regenerative medicine applications. Herein, we demonstrate two potential ways to immunoassist the remodeling process of engineered soft tissues in three-dimensional (3-D) gelatin based hydrogels containing fibroblasts and/or endothelial Cells: (i) with supplementation of interleukin-4 (IL-4) in the presence of macrophages and (ii) in tri-culture via naive monocytes or differentiated macrophages. The presence of IL-4 had a proliferative effect on fibroblasts, with a significant boosting effect on proliferation and cytokine secretion in the presence of differentiated macrophages with an upregulation of activin, interleukin-1 receptor antagonist (IL-1RA), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β), creating a more stimulating microenvironment. The addition of IL-4 in endothelial Cell/macrophage co-culture configuration improved the organization of the sprout-like structures, with a boost in proliferation at day 1 and with an upregulation of IL-6 and IL-1RA at the earliest stage in the presence of differentiated macrophages creating a favorable microenvironment for angiogenesis. In tri-culture conditions, the presence of monocytes or macrophages resulted in a denser tissue-like structure with highly remodeled hydrogels. The presence of differentiated macrophages had a boosting effect on the angiogenic secretory microenvironment, such as IL-6 and IL-8, without any additional cytokine supplementation. The presence of fibroblasts in combination with endothelial Cells also had a significant effect on the secretion of angiopoietin. Our results demonstrate that incorporation of macrophages in a resident macrophage function and their phenoType control have significant effects on the maturation and cytokine microenvironment of 3-D Multiple Cell Type-laden hydrogels, which can be harnessed for better integration of implantable systems and for more physiologically relevant in vitro tissue models with an immune component
Julien Barthes - One of the best experts on this subject based on the ideXlab platform.
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incorporation of resident macrophages in engineered tissues Multiple Cell Type response to microenvironment controlled macrophage laden gelatine hydrogels
Journal of Tissue Engineering and Regenerative Medicine, 2018Co-Authors: Camille Dollinger, Sait Ciftci, Helena Knopfmarques, Rabia Guner, Amir M Ghaemmaghami, Christian Debry, Julien Barthes, Nihal Engin VranaAbstract:The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key Cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, an in-vitro model of interaction was developed between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming Cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, naive THP-1 monocytes, endothelial Cells and fibroblasts were seeded on the gels as incoming Cells. The interaction was first monitored in the absence of the gels. To mimic resident macrophages, THP-1 Cells were encapsulated in the presence or absence of IL-4 to control their phenoType and then these hydrogels were seeded with incoming Cells. Without encapsulation, activated macrophages induce apoptosis in endothelial Cells. Once encapsulated no adverse effects were seen. Macrophage-laden hydrogels attracted more endothelial Cells and fibroblasts compared to monocytes-laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted Cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in more secretion of both pro- and anti-inflammatory cytokines compared to M2 stimulation. It was demonstrated that there is a distinct effect of encapsulated macrophages on the behaviour of the incoming Cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation.
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Table_1_Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation.docx
2018Co-Authors: Julien Barthes, Camille Dollinger, Celine B. Muller, Urmas Liivas, Agnes Dupret-bories, Helena Knopf-marques, Nihal E. VranaAbstract:The function of soft tissues is intricately linked to their connections with the other systems of the body such as circulation, nervous system, and immune system. The presence of resident macrophages in tissues provides a means to control tissue homeostasis and also a way to react to the physical/biological insults and tissue damage. Thus, incorporation of resident macrophage like phenoType-controlled macrophages in engineered tissues can improve their fidelity as model tissues and also improve their rate of integration and facilitate the resolution of inflammation for regenerative medicine applications. Herein, we demonstrate two potential ways to immunoassist the remodeling process of engineered soft tissues in three-dimensional (3-D) gelatin based hydrogels containing fibroblasts and/or endothelial Cells: (i) with supplementation of interleukin-4 (IL-4) in the presence of macrophages and (ii) in tri-culture via naive monocytes or differentiated macrophages. The presence of IL-4 had a proliferative effect on fibroblasts, with a significant boosting effect on proliferation and cytokine secretion in the presence of differentiated macrophages with an upregulation of activin, interleukin-1 receptor antagonist (IL-1RA), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β), creating a more stimulating microenvironment. The addition of IL-4 in endothelial Cell/macrophage co-culture configuration improved the organization of the sprout-like structures, with a boost in proliferation at day 1 and with an upregulation of IL-6 and IL-1RA at the earliest stage in the presence of differentiated macrophages creating a favorable microenvironment for angiogenesis. In tri-culture conditions, the presence of monocytes or macrophages resulted in a denser tissue-like structure with highly remodeled hydrogels. The presence of differentiated macrophages had a boosting effect on the angiogenic secretory microenvironment, such as IL-6 and IL-8, without any additional cytokine supplementation. The presence of fibroblasts in combination with endothelial Cells also had a significant effect on the secretion of angiopoietin. Our results demonstrate that incorporation of macrophages in a resident macrophage function and their phenoType control have significant effects on the maturation and cytokine microenvironment of 3-D Multiple Cell Type-laden hydrogels, which can be harnessed for better integration of implantable systems and for more physiologically relevant in vitro tissue models with an immune component.
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Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation
Frontiers Media S.A., 2018Co-Authors: Camille Dollinger, Julien Barthes, Celine B. Muller, Urmas Liivas, Agnes Dupret-bories, Helena Knopf-marques, Nihal E. VranaAbstract:The function of soft tissues is intricately linked to their connections with the other systems of the body such as circulation, nervous system, and immune system. The presence of resident macrophages in tissues provides a means to control tissue homeostasis and also a way to react to the physical/biological insults and tissue damage. Thus, incorporation of resident macrophage like phenoType-controlled macrophages in engineered tissues can improve their fidelity as model tissues and also improve their rate of integration and facilitate the resolution of inflammation for regenerative medicine applications. Herein, we demonstrate two potential ways to immunoassist the remodeling process of engineered soft tissues in three-dimensional (3-D) gelatin based hydrogels containing fibroblasts and/or endothelial Cells: (i) with supplementation of interleukin-4 (IL-4) in the presence of macrophages and (ii) in tri-culture via naive monocytes or differentiated macrophages. The presence of IL-4 had a proliferative effect on fibroblasts, with a significant boosting effect on proliferation and cytokine secretion in the presence of differentiated macrophages with an upregulation of activin, interleukin-1 receptor antagonist (IL-1RA), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β), creating a more stimulating microenvironment. The addition of IL-4 in endothelial Cell/macrophage co-culture configuration improved the organization of the sprout-like structures, with a boost in proliferation at day 1 and with an upregulation of IL-6 and IL-1RA at the earliest stage in the presence of differentiated macrophages creating a favorable microenvironment for angiogenesis. In tri-culture conditions, the presence of monocytes or macrophages resulted in a denser tissue-like structure with highly remodeled hydrogels. The presence of differentiated macrophages had a boosting effect on the angiogenic secretory microenvironment, such as IL-6 and IL-8, without any additional cytokine supplementation. The presence of fibroblasts in combination with endothelial Cells also had a significant effect on the secretion of angiopoietin. Our results demonstrate that incorporation of macrophages in a resident macrophage function and their phenoType control have significant effects on the maturation and cytokine microenvironment of 3-D Multiple Cell Type-laden hydrogels, which can be harnessed for better integration of implantable systems and for more physiologically relevant in vitro tissue models with an immune component
Toshio Fukuda - One of the best experts on this subject based on the ideXlab platform.
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fabrication of perfusable 3d hepatic lobule like constructs through assembly of Multiple Cell Type laden hydrogel microstructures
Biofabrication, 2018Co-Authors: Juan Cui, Huaping Wang, Zhiqiang Zheng, Qing Shi, Tao Sun, Qiang Huang, Toshio FukudaAbstract:The in vitro reproduction of three-dimensional (3D) Cellular constructs to physiologically mimic human liver is highly desired for drug screening and clinical research. However, the fabrication of a liver-mimetic 3D model using traditional bottom-up technologies is challenging owing to the complex architecture and specific functions of real liver tissue. This work proposes a versatile strategy for spatially assembling gear-like microstructures encapsulating Multiple Cell Types, and reorganizing them into 3D lobule-like micro-architecture with physiological relevance to native liver tissue. Gear-like microstructures were fabricated by photo-crosslinking poly(ethylene glycol) diacrylate (PEGDA) hydrogel mixed with hepatocytes and fibroblasts, in a digital micromirror device (DMD)-based microfluidic channel. The microstructures were assembled through coordinated micromanipulation based on local fluid force, and spatially self-aligned through hydrophilic-hydrophobic interactions into a 3D integrated construct with lobule-like morphology and a perfusable central lumen. The resulting 3D lobule-like constructs allowed long-term co-culture of hepatocytes and fibroblasts with high Cell viability. The co-cultured constructs enhanced hepatocyte proliferation and spreading, as well as liver functions including a 50% increase in albumin secretion and urea synthesis. For hepatotoxicity assessment, the 3D lobule-like construct enabled drug perfusion through its built-in lumen for simulation of drug diffusion in the liver, which could improve the response sensitivity and efficiency to hepatotoxic drug. These results demonstrated that this method provides a valuable 3D co-culture model with perfusable lobule-like architecture and physiological functions, which has potential applications in drug discovery and tissue engineering applications.
William P Tansey - One of the best experts on this subject based on the ideXlab platform.
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Multiple Cell Type specific elements regulate myc protein stability
Oncogene, 2004Co-Authors: Andreas Herbst, Simone E Salghetti, So Young Kim, William P TanseyAbstract:Myc is a highly unstable transcription factor that is destroyed by ubiquitin (Ub)-mediated proteolysis. We have previously identified an amino-terminal 'degron' within Myc that signals its destruction; this degron spans the transcriptional activation domain of Myc, and includes two highly conserved regions called Myc boxes I and II. We now report the identification of a second element--the D-element--which is also required for Myc proteolysis. The centrally located D-element is distinct from the PEST domain in Myc, but includes Myc box III, a third highly conserved region with no previously known function. We show that deletion of the D-element stabilizes the Myc protein without affecting its ubiquitylation, and report that the D-element and the degron act in a Cell-Type-specific manner to direct Myc proteolysis. These data thus demonstrate that Myc stability is regulated at both the ubiquitylation and postubiquitylation levels, and reveal that substrates of the Ub-proteasome system can be targeted for destruction differently in different Cell Types.