The Experts below are selected from a list of 1542 Experts worldwide ranked by ideXlab platform
Martin L Yarmush - One of the best experts on this subject based on the ideXlab platform.
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metabolic patterning on a chip towards in vitro Liver zonation of primary rat and human hepatocytes
Scientific Reports, 2018Co-Authors: Young Bok Abraham Kang, Martin L Yarmush, Safak Mert, Berk O UstaAbstract:An important number of healthy and diseased tissues shows spatial variations in their metabolic capacities across the tissue. The Liver is a prime example of such heterogeneity where the gradual changes in various metabolic activities across the Liver Sinusoid is termed as “zonation” of the Liver. Here, we introduce the Metabolic Patterning on a Chip (MPOC) platform capable of dynamically creating metabolic patterns across the length of a microchamber of Liver tissue via actively enforced gradients of various metabolic modulators such as hormones and inducers. Using this platform, we were able to create continuous Liver tissues of both rat and human origin with gradually changing metabolic activities. The gradients we have created in nitrogen, carbohydrate and xenobiotic metabolisms recapitulated an in vivo like zonation and zonal toxic response. Beyond its application in recapitulation of Liver zonation in vitro as we demonstrate here, the MPOC platform can be used and expanded for a variety of purposes including better understanding of heterogeneity in many different tissues during developmental and adult stages.
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long term maintenance of a microfluidic 3d human Liver Sinusoid
Biotechnology and Bioengineering, 2016Co-Authors: Ljupcho Prodanov, Rohit Jindal, Shyam Sundhar Bale, Manjunath Hegde, William J Mccarty, Inna Golberg, Abhinav Bhushan, Martin L Yarmush, Osman Berk UstaAbstract:The development of long-term human organotypic Liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA's initiative to replicate and replace chronic and acute drug testing in animals. For this purpose, we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a Liver Sinusoid-on-a-chip, using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the Liver Sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic) and urea excretion (detoxification) were observed under flow compared to static cultures. This human Liver-on-a-chip should be further evaluated in drug-related studies.
Young Bok Abraham Kang - One of the best experts on this subject based on the ideXlab platform.
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metabolic patterning on a chip towards in vitro Liver zonation of primary rat and human hepatocytes
Scientific Reports, 2018Co-Authors: Young Bok Abraham Kang, Martin L Yarmush, Safak Mert, Berk O UstaAbstract:An important number of healthy and diseased tissues shows spatial variations in their metabolic capacities across the tissue. The Liver is a prime example of such heterogeneity where the gradual changes in various metabolic activities across the Liver Sinusoid is termed as “zonation” of the Liver. Here, we introduce the Metabolic Patterning on a Chip (MPOC) platform capable of dynamically creating metabolic patterns across the length of a microchamber of Liver tissue via actively enforced gradients of various metabolic modulators such as hormones and inducers. Using this platform, we were able to create continuous Liver tissues of both rat and human origin with gradually changing metabolic activities. The gradients we have created in nitrogen, carbohydrate and xenobiotic metabolisms recapitulated an in vivo like zonation and zonal toxic response. Beyond its application in recapitulation of Liver zonation in vitro as we demonstrate here, the MPOC platform can be used and expanded for a variety of purposes including better understanding of heterogeneity in many different tissues during developmental and adult stages.
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Liver Sinusoid on a chip long term layered co culture of primary rat hepatocytes and endothelial cells in microfluidic platforms
Biotechnology and Bioengineering, 2015Co-Authors: Young Bok Abraham Kang, Temitope R Sodunke, Jason Lamontagne, Joseph Cirillo, Caroline Rajiv, Michael J Bouchard, Moses NohAbstract:We describe the generation of microfluidic platforms for the co-culture of primary hepatocytes and endothelial cells; these platforms mimic the architecture of a Liver Sinusoid. This paper describes a progressional study of creating such a Liver Sinusoid on a chip system. Primary rat hepatocytes (PRHs) were co-cultured with primary or established endothelial cells in layers in single and dual microchannel configurations with or without continuous perfusion. Cell viability and maintenance of hepatocyte functions were monitored and compared for diverse experimental conditions. When primary rat hepatocytes were co-cultured with immortalized bovine aortic endothelial cells (BAECs) in a dual microchannel with continuous perfusion, hepatocytes maintained their normal morphology and continued to produce urea for at least 30 days. In order to demonstrate the utility of our microfluidic Liver Sinusoid platform, we also performed an analysis of viral replication for the hepatotropic hepatitis B virus (HBV). HBV replication, as measured by the presence of cell-secreted HBV DNA, was successfully detected. We believe that our Liver model closely mimics the in vivo Liver Sinusoid and supports long-term primary Liver cell culture. This Liver model could be extended to diverse Liver biology studies and Liver-related disease research such as drug induced Liver toxicology, cancer research, and analysis of pathological effects and replication strategies of various hepatotropic infectious agents. .
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layered long term co culture of hepatocytes and endothelial cells on a transwell membrane toward engineering the Liver Sinusoid
Biofabrication, 2013Co-Authors: Young Bok Abraham Kang, Joseph Cirillo, Michael J Bouchard, Siddhartha Rawat, Hongseok NohAbstract:This paper presents a novel Liver model that mimics the Liver Sinusoid where most Liver activities occur. A key aspect of our current Liver model is a layered co-culture of primary rat hepatocytes (PRHs) and primary rat Liver Sinusoidal endothelial cells (LSECs) or bovine aortic endothelial cells (BAECs) on a transwell membrane. When a layered co-culture was attempted with a thin Matrigel layer placed between hepatocytes and endothelial cells to mimic the space of Disse, the cells did not form completely separated monolayers. However, when hepatocytes and endothelial cells were cultured on the opposite sides of a transwell membrane, PRHs co-cultured with LSECs or BAECs maintained their viability and normal morphology for 39 and 57 days, respectively. We assessed the presence of hepatocyte-specific differentiation markers to verify that PRHs remained differentiated in the long-term co-culture and analyzed hepatocyte function by monitoring urea synthesis. We also noted that the expression of cytochrome P-450 remained similar in the co-cultured system from day 1 to day 48. Thus, our novel Liver model system demonstrated that primary hepatocytes can be cultured for extended times and retain their hepatocyte-specific functions when layered with endothelial cells.
Luke P Lee - One of the best experts on this subject based on the ideXlab platform.
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an artificial Liver Sinusoid with a microfluidic endothelial like barrier for primary hepatocyte culture
Biotechnology and Bioengineering, 2007Co-Authors: Philip J Lee, Paul J Hung, Luke P LeeAbstract:Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial Liver Sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the Liver acinus. This unit consisted of a cord of hepatocytes (50 x 30 x 500 microm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min). This configuration sustained rat and human hepatocytes for 7 days without an extracellular matrix (ECM) coating. Experiments with the metabolism mediated Liver toxicant diclofenac showed no hepatotoxicity after 4 h and an IC(50) of 334 +/- 41 microM after 24 h.
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an artificial Liver Sinusoid with a microfluidic endothelial like barrier for primary hepatocyte culture
Biotechnology and Bioengineering, 2007Co-Authors: Philip J Lee, Paul J Hung, Luke P LeeAbstract:Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial Liver Sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the Liver acinus. This unit consisted of a cord of hepatocytes (50 × 30 × 500 µm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min). This configuration sustained rat and human hepatocytes for 7 days without an extracellular matrix (ECM) coating. Experiments with the metabolism mediated Liver toxicant diclofenac showed no hepatotoxicity after 4 h and an IC50 of 334 ± 41 µM after 24 h. Biotechnol. Bioeng. 2007; 97: 1340–1346. © 2007 Wiley Periodicals, Inc.
Valérie Costes - One of the best experts on this subject based on the ideXlab platform.
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Indolent cytotoxic T cell lymphoproliferation associated with nodular regenerative hyperplasia: a common Liver lesion in the context of common variable immunodeficiency disorder
Virchows Archiv, 2015Co-Authors: Vanessa Szablewski, Céline René, Valérie CostesAbstract:Patients with common variable immunodeficiency disorder (CVID) are subject to lymphoproliferative disorders and predisposed to lymphoma. Some patients may also develop Liver lesions. The purpose of this study was to define clinical and histopathological features of patients with CVID presenting with Liver lesions suspicious of lymphoma. Four CVID cases corresponding to these criteria were retrieved from our files. Liver biopsy specimens were subjected to morphologic, immunophenotypic and molecular analysis. All patients presented with hepatosplenomegaly and two furthermore with lymphadenopathy. The clinical working diagnosis in the four cases was lymphoma. All Liver biopsies revealed nodular regenerative hyperplasia (NRH), associated with mild to marked Sinusoid lymphocytic infiltrate consisting of "activated" cytotoxic T cells (CD8+, Tia1+, granzyme B+, TCRβF1+, CD56-). EBER was negative in all cases. T cell clonality was found in one of the two interpretable cases. All patients had an indolent course and clinical symptoms regressed with immunoglobulin replacement. This study suggests that indolent proliferation in the Liver Sinusoid of cytotoxic T cell associated with NRH is a specific Liver lesion in the context of CVID. In CVID patients clinically suspected of lymphoma, pathologists should avoid a misdiagnosis of aggressive T cell lymphoma with a risk of over treatment.
Philip J Lee - One of the best experts on this subject based on the ideXlab platform.
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an artificial Liver Sinusoid with a microfluidic endothelial like barrier for primary hepatocyte culture
Biotechnology and Bioengineering, 2007Co-Authors: Philip J Lee, Paul J Hung, Luke P LeeAbstract:Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial Liver Sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the Liver acinus. This unit consisted of a cord of hepatocytes (50 x 30 x 500 microm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min). This configuration sustained rat and human hepatocytes for 7 days without an extracellular matrix (ECM) coating. Experiments with the metabolism mediated Liver toxicant diclofenac showed no hepatotoxicity after 4 h and an IC(50) of 334 +/- 41 microM after 24 h.
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an artificial Liver Sinusoid with a microfluidic endothelial like barrier for primary hepatocyte culture
Biotechnology and Bioengineering, 2007Co-Authors: Philip J Lee, Paul J Hung, Luke P LeeAbstract:Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial Liver Sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the Liver acinus. This unit consisted of a cord of hepatocytes (50 × 30 × 500 µm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min). This configuration sustained rat and human hepatocytes for 7 days without an extracellular matrix (ECM) coating. Experiments with the metabolism mediated Liver toxicant diclofenac showed no hepatotoxicity after 4 h and an IC50 of 334 ± 41 µM after 24 h. Biotechnol. Bioeng. 2007; 97: 1340–1346. © 2007 Wiley Periodicals, Inc.