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Transdifferentiation of Pancreatic Cells to Hepatocytes

Hepatocytes maintained in culture provide an attractive model system for the study of liver function. Furthermore, hepatocyte transplantation offers an alternative cellular therapy to orthotopic liver transplantation for the treatment of hepatic failure and hereditary li ...

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Evaluation of Drug Metabolism, DrugDrug Interactions, and In Vitro Hepatotoxicity with Cryopreserved Human Hepatocytes

Human-based in vitro hepatic experimental systems are now used routinely in drug development. The initial concept of the use of human-based in vitro systems is based on the known species–species differences in drug properties. Human-specific drug properties, by definition, cannot be de ...

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The Use of Human Hepatocytes to Investigate Drug Metabolism and CYP Enzyme Induction

Over the past two decades, attrition of new drug candidates which entered into development increased strongly mainly due to sub-optimal ADME profiles. Major problems were linked to poor metabolic stability and drug–drug interactions linked to inhibition or induction of metabolism. ...

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The Use of Hepatocytes to Investigate UDP-Glucuronosyltransferases and Sulfotransferases

Since phase II reactions quantitatively represent the most important pathways involved in drug biotransformation, the development and the use of in vitro approaches to predict glucuronidation and sulfation are currently attracting intense interest to assist in the selection of ...

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Metabonomic Studies on Human Hepatocyte in Primary Culture

Mechanisms involved in induction processes have been investigated using fresh human hepatocytes in culture as a cellular model and using mass spectrometry-based metabonomics as a global investigation tool. Sample preparation to data analysis have been detailed in an approach ena ...

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The Use of Hepatocytes to Investigate Drug Uptake Transporters

The liver plays an important role in the clearance of endogenous and exogenous compounds, including drugs. As hepatic uptake is the first step in hepatic clearance, any change in the former process directly affects the overall intrinsic hepatic clearance. Several uptake transporters are ...

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Hepatic Stem Cells

Early studies in hepatocyte turnover and liver regeneration showed that the parenchymal cell, the hepatocyte, was the primary and only cell involved in tissue renewal. However, new studies of liver regeneration, hepatocarcinogenesis, liver transplantation, and various cell lin ...

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Markers and Signaling Factors for Stem Cell Differentiation to Hepatocytes: Lessons from Developmental Studies

Liver transplantation is the preferred option to treat a number of hepatic diseases in adults and children, but the number of patients on the waiting list is exceeding the number of available livers for transplantation. Hepatocytes differentiated in vitro from stem cells are a promising and r ...

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Reversible Manipulation of Apoptosis Sensitivity in Cultured Hepatocytes by Matrix-Mediated Manipulation of Signaling Activities

Hepatocytes in culture are a valuable tool to investigate mechanisms involved in the response of the liver to cytokines. However, it is well established that hepatocytes cultured as monolayers on dried stiff collagen dedifferentiate, loosing specialized liver functions. In contra ...

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Hepatocyte Differentiation

Increasingly, research suggests that for certain systems, animal models are insufficient for human toxicology testing. The development of robust, in vitro models of human toxicity is required to decrease our dependence on potentially misleading in vivo animal studies. A critical de ...

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Cryopreservation of Human Hepatocytes for Clinical Use

Cryopreservation of hepatocytes is important for use both in research and for clinical application in hepatocyte transplantation. Cryopreservation causes damage to hepatocytes with the result that cell viability and function is reduced on thawing compared to fresh cells. There a ...

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Using In Situ Hybridisation to Localize Renal Gene Expression in Tissue Sections

The basics of in situ hybridization have been widely applied to a diverse range of situations where we need to localize the distribution of nucleic acids. Advances in other molecular techniques such as the advent of gene microarrays has not diminished the significance of in situ hybridization, ...

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In Vivo Imaging of Leukocyte Recruitment to Glomeruli in Mice Using Intravital Microscopy

Leukocytes mediate some forms of glomerulonephritis, particularly severe proliferative and crescentic forms. The renal glomerulus is one of the few sites within the microvasculature in which leukocyte recruitment occurs in capillaries. However, due to the difficulty of direct ...

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Quantitative Gene Expression Analysis in Kidney Tissues

Quantitative gene expression analysis is fundamental to many experimental protocols and hypothesis testing in scientific research. The most popular currently used method to measure the expression level of specific genes in biological samples is real-time quantitative polym ...

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Laser Capture Microdissection of Kidney Tissue

Kidney tissue laser capture microdissection (LCM) is of great clinical relevance since genome wide studies on total kidney messenger RNA (mRNA) potentially miss important factors involved in the pathogenesis of the disease in glomeruli and tubules. This technique is readily applic ...

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Measurement of Glomerular Filtration Rate in Conscious Mice

Glomerular filtration rate (GFR) is an important index of renal function and routinely used in patient care and basic research to evaluate progression of renal diseases or test the efficacy of novel therapeutic strategies. Determination of GFR in mouse models has been mostly practiced in an ...

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In Vivo Transfer of Small Interfering RNA or Small Hairpin RNA Targeting Glomeruli

Small synthetic interfering RNA duplexes (siRNAs) can selectively suppress gene expression in somatic mammalian cells without the nonselective toxic effects associated with double-stranded RNA (dsRNA). However, in vivo delivery of siRNA targeting the kidney has been describ ...

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SELDI-TOF Mass Spectrometry-Based Protein Profiling of Kidney Tissue

Protein profiling has numerous applications in renal research including the detection of protein biomarkers with aberrant expression levels during disease development. Such information is essential for early diagnosis and will aid the improvement of patient management and m ...

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Determination of Collagen Content, Concentration, and Sub-types in Kidney Tissue

Fibrosis and sclerosis are widely recognized as hallmarks of progressive renal disease and are caused by the excessive accumulation of connective tissue, mostly collagen. The detection of collagen content, concentration (collagen content/dry weight tissue), and sub-types from ...

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Mechanical Stretch-Induced Signal Transduction in Cultured Mesangial Cells

The investigation of the effects of mechanical stretch on mesangial cells can provide important insights into glomerular pathophysiology related to increased intraglomerular pressure (Pgc). Elevated Pgc, leading to the transmission of abnormal mechanical stress to reside ...

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