Extracorporeal Perfusion for the Treatment of Acute Liver Failure

Stockmann, H.B.A.C.; Hiemstra, Coen A.; Marquet, R. L.; Ijzermans, J. N. M.

doi:10.1097/00000658-200004000-00003

Cited by 77 publications

(42 citation statements)

References 86 publications

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“…One of the most important aspects of mammalian cell culture for the purpose of reconstructing tissues is the necessity to use specialized cell types requiring specific culture conditions that induce differentiated functions. For example, hepatocytes are the key component of bioartificial liver assist devices, which are meant to provide temporary support to patients undergoing life-threatening acute liver failure (Busse et al, 1999;Hui et al, 2001;Stockmann et al, 2000;Tzanakakis et al, 2000). Many studies on cultured hepatocytes focus on the effect of culture conditions on the major liver-specific functions believed to be critical in the operation of a bioartificial liver device (e.g., urea synthesis and cytochrome P450 activities) as well as marker functions indicative of a differentiated state of the cell (e.g., synthesis of albumin and transferrin) .…”

Section: Introductionmentioning

confidence: 99%

Metabolic flux analysis of cultured hepatocytes exposed to plasma

Chan

Berthiaume

Lee

et al. 2002

Biotech & Bioengineering

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Hepatic metabolism can be investigated using metabolic flux analysis (MFA), which provides a comprehensive overview of the intracellular metabolic flux distribution. The characterization of intermediary metabolism in hepatocytes is important for all biotechnological applications involving liver cells, including the development of bioartificial liver (BAL) devices. During BAL operation, hepatocytes are exposed to plasma or blood from the patient, at which time they are prone to accumulate intracellular lipids and exhibit poor liver-specific functions. In a prior study, we found that preconditioning the primary rat hepatocytes in culture medium containing physiological levels of insulin, as opposed to the typical supraphysiological levels found in standard hepatocyte culture media, reduced lipid accumulation during subsequent plasma exposure. Furthermore, supplementing the plasma with amino acids restored hepatospecific functions. In the current study, we used MFA to quantify the changes in intracellular pathway fluxes of primary rat hepatocytes in response to low-insulin preconditioning and amino acid supplementation. We found that culturing hepatocytes in medium containing lower physiological levels of insulin decreased the clearance of glucose and glycerol with a concomitant decrease in glycolysis. These findings are consistent with the general notion that low insulin, especially in the presence of high glucagon levels, downregulates glycolysis in favor of gluconeogenesis in hepatocytes. The MFA model shows that, during subsequent plasma exposure, low-insulin preconditioning upregulated gluconeogenesis, with lactate as the primary precursor in unsupplemented plasma, with a greater contribution from deaminated amino acids in amino acid-supplemented plasma. Concomitantly, low-insulin preconditioning increased fatty acid oxidation, an effect that was further enhanced by amino acid supplementation to the plasma. The increase in fatty acid oxidation reduced intracellular triglyceride accumulation. Overall, these findings are consistent with the notion that the insulin level in medium culture presets the metabolic machinery of hepatocytes such that it directly impacts on their metabolic behavior during subsequent plasma culture.

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Section: Introductionmentioning

confidence: 99%

Metabolic flux analysis of cultured hepatocytes exposed to plasma

Chan

Berthiaume

Lee

et al. 2002

Biotech & Bioengineering

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“…The high mortality rate because of liver deformities that led to 1.4 million deaths annually has not been avoided by liver transplantation which is the most efficient therapy so far [68]. In addition to stem cell mobilizing strategies [56] and bioartificial liver devices (BAL) [78], several alternative cell-based therapies have been investigated to recover unstable conditions in chronic liver disorders as well as during metabolic or acute liver failure. In general the disorders are treated by transplantation of bone marrow hematopoietic, mesenchymal, and mononuclear cell populations (for review see [93] and [74]).…”

Section: Mscs In Liver Regenerationmentioning

confidence: 99%

Engineered MSCs from Patient-Specific iPS Cells

Eberle

Moslem

Henschler

et al. 2012

Mesenchymal Stem Cells - Basics and Clinical Application II

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Mesenchymal stroma/stem cells (MSCs) represent a heterogenic cell population that can be isolated from various tissues of the body or can be generated from pluripotent stem cells by in vitro differentiation. Various promising pre-clinical and clinical studies suggest that MSCs might stimulate endogenous regeneration and/or act as anti-inflammatory agents, which could be of high therapeutic relevance for a number of diseases, including graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, inflammatory bowel diseases, or some forms of liver failure. Notably, conflicting results of various studies illustrated that the source of MSCs, the cultivation condition, and the way of administration have important effects on the desired clinical effect. Some of the involved molecular pathways have recently been elucidated and an artificial modulation of these pathways by engineered MSCs might result in superfunctional MSCs for enhanced endogenous regeneration or anti-inflammatory response. In this review, we summarize important findings of conventional MSCs for applications in gastroenterology and we describe the state-of-the-art for the generation of patient-derived iPS cells that eventually might provide genetically engineered superfunctional iPS cells for advanced cell therapies.

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“…Bioartificial or hybrid devices combine the best of both biological and non-biological techniques. [17][18][19][20] Because most of the data with regard to extracorporeal liver support are available for non-biological support systems, we will further focus on these techniques.…”

Section: Which Types Of Liver Support Are Available?mentioning

confidence: 99%

Review article: non‐biological liver support in liver failure

Laleman¹,

Wilmer²,

Evenepoel³

et al. 2006

Aliment Pharmacol Ther

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SUMMARYLiver failure, whether acute or acute-on-chronic, remains an important cause of morbidity and mortality. The lack of liver detoxification, metabolic and regulatory functions of the liver leads to life-threatening complications, such as renal failure, altered immune response, hepatic coma and systemic haemodynamic dysfunction, eventually culminating in multiorgan failure.Current medical therapy involves the management of the precipitating event and treatment of complications until the liver eventually recovers, leaving us with no other treatment options than transplantation if these attempts fail. However, the shortage in cadaveric organs and other transplant-related problems, have prompted the need for alternative methods to provide liver support.As liver failure is often potentially reversible, considerable effort has been invested in the development of liver support systems. Currently, most of the experience is available for non-biological support systems. They represent the focus of this review, which aims to define the goals of liver support, to describe the design of the different existing devices and to analyse the available data to determine their current status in the management of patients with liver failure.

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Extracorporeal Perfusion for the Treatment of Acute Liver Failure

Cited by 77 publications

References 86 publications

Metabolic flux analysis of cultured hepatocytes exposed to plasma

Metabolic flux analysis of cultured hepatocytes exposed to plasma

Engineered MSCs from Patient-Specific iPS Cells

Review article: non‐biological liver support in liver failure

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