Review: Artificial liver support systems

Kamlot, Andreas; Rózga, Jacek; Watanabe, F.; Demetriou, Achilles A.

doi:10.1002/(sici)1097-0290(19960520)50:4<382::aid-bit5>3.0.co;2-h

Cited by 35 publications

(13 citation statements)

References 54 publications

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“…However, as previously mentioned, only $10% of the ECS volume was filled with hepatocytes during the experimental study. Utilizing this low hepatocyte density, an enormous number ($250) of hollow fiber bioreactors operating in parallel would be required in order to reach the desired minimum of 20% of the in vivo hepatocyte mass necessary to sustain an ALF patient (10-40% of the liver mass has been reported to be essential for maintaining proper liver function [7,[34][35][36]). For this reason, the model was also utilized to predict operating conditions with more feasible cell numbers, flow rates, and bRBC concentrations.…”

Section: Ecs Zonationmentioning

confidence: 99%

Enhanced Oxygen Delivery to Primary Hepatocytes within a Hollow Fiber Bioreactor Facilitated via Hemoglobin-Based Oxygen Carriers

Sullivan

Gordon

Bou‐Akl

et al. 2007

Artificial Cells, Blood Substitutes, and Biotechnology

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The production of a fully functional bioartificial liver assist device (BLAD) would greatly enhance available treatment options for patients suffering from acute liver failure. Currently, inadequate oxygen provision to hepatocytes seeded within hollow fiber bioreactors hampers development of a viable hollow fiber-based BLAD. Experimentally, oxygen provision to primary rat hepatocytes cultured within hollow fiber bioreactors was measured, it was observed that supplementation with an oxygen carrier (bovine red blood cells at approximately 2% human hematocrit) did not significantly improve oxygenation compared to the absence of an oxygen carrier. Therefore, an oxygen transport model of an individual hollow fiber within the bioreactor was developed and simulated (up to approximately 10% human hematocrit) to more fully examine the effect of oxygen carrier supplementation on oxygenation within the bioreactor. The modeling analysis, supported via the experimental results, was utilized to predict optimal bioreactor operating conditions for the delivery of in vivo-like oxygen gradients to cultured hepatocytes in clinically relevant settings.

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Section: Ecs Zonationmentioning

confidence: 99%

Enhanced Oxygen Delivery to Primary Hepatocytes within a Hollow Fiber Bioreactor Facilitated via Hemoglobin-Based Oxygen Carriers

Sullivan

Gordon

Bou‐Akl

et al. 2007

Artificial Cells, Blood Substitutes, and Biotechnology

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“…14 -16 Ideally, an artificial liver system should stabilize a patient, improve his or her general condition, and decrease the operative and perioperative risks of liver transplantation. 17,18 It was recently reported that a multicellular spheroid composed of adult rat hepatocytes exhibited high albumin secretion, and it effectively maintained the same morphological state as in vivo liver tissue. The rapid formation of spherical multicellular hepatocyte spheroids and the expression of liver-specific functions are important in developing a hybrid artificial liver.…”

Section: Introductionmentioning

confidence: 98%

Evaluation of a galactose‐carrying gelatin sponge for hepatocytes culture and transplantation

Hong

Lee

Akaike

2003

J Biomedical Materials Res

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This study proposes a new three-dimensional culture of mouse hepatocytes in a porous galactose-carrying modified gelatin sponge matrix. The modification of gelatin using galactose residues significantly increased the attachment of hepatocytes on the substrate. A modified gelatin sponge with lactobionic acid (MGLA) was prepared to increase the specific interaction between the hepatocytes and the matrix. Hepatocytes cultured in a three-dimensional MGLA sponge released much less lactate dehydrogenase than those cultured on a collagen Type I-coated monolayer. Moreover, the survival rate of hepatocytes cultured on an MGLA sponge was longer than the survival rate of hepatocytes cultured on a collagen Type I-coated monolayer. Hepatic specific metabolic functions, namely, the secretion of serum albumin and the synthesis of urea, were well maintained and promoted by spheroidal hepatocytes formed in the MGLA sponge.

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“…Unfortunately, because the number of patients requiring liver transplant surgery far exceeds the available supply of donor livers, 1,2 patients on the waiting list will die unless alternative therapies are employed. Although unable to duplicate the full range of liver functions, devices able to perform key liver functions have been developed-such as charcoal filters for ammonia detoxification, 3 molecular adsorbents to facilitate removal of protein-bound toxic metabolites, 4 and bioartificial liver (BAL) devices. [5][6][7] Of the variety of BAL designs that exist (e.g., flat plate, hollow fiber [HF], microcarrier-based, etc.…”

Section: Introductionmentioning

confidence: 99%

Effects of Enhanced O₂ Transport on Hepatocytes Packed within a Bioartificial Liver Device

McClelland

Coger²

2004

Tissue Engineering

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The functional performance of an extracorporeal bioartificial liver (BAL) device requires that suitable nutrient pathways exist to support the hepatocytes packed within it. Consequently the limited transport distance of the nutrient oxygen is a limiting factor in the scale-up of many BAL designs. In this study the porosity of a collagen extracellular matrix is increased to evaluate how enhanced O(2) transport alters the viability and functional performance of gel-entrapped hepatocytes packed within a BAL. Our results indicate that the porous collagen increases the number of viable hepatocytes that can be supported by a single O(2) source. Furthermore, the results illustrate that, compared with normal collagen, porous collagen extends the O(2) transport distance such that hepatocytes located at larger distances from the O(2) source of the BAL can be supported. Finally, the function results reveal that hepatocytes within the porous collagen experience significantly improved function over the control cultures. Hence our results demonstrate that enhancing O(2) transport through the extracellular matrix of densely packed BAL designs is one way to significantly improve the functionality of these devices.

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Review: Artificial liver support systems

Cited by 35 publications

References 54 publications

Enhanced Oxygen Delivery to Primary Hepatocytes within a Hollow Fiber Bioreactor Facilitated via Hemoglobin-Based Oxygen Carriers

Enhanced Oxygen Delivery to Primary Hepatocytes within a Hollow Fiber Bioreactor Facilitated via Hemoglobin-Based Oxygen Carriers

Evaluation of a galactose‐carrying gelatin sponge for hepatocytes culture and transplantation

Effects of Enhanced O₂ Transport on Hepatocytes Packed within a Bioartificial Liver Device

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Review: Artificial liver support systems

Cited by 35 publications

References 54 publications

Enhanced Oxygen Delivery to Primary Hepatocytes within a Hollow Fiber Bioreactor Facilitated via Hemoglobin-Based Oxygen Carriers

Enhanced Oxygen Delivery to Primary Hepatocytes within a Hollow Fiber Bioreactor Facilitated via Hemoglobin-Based Oxygen Carriers

Evaluation of a galactose‐carrying gelatin sponge for hepatocytes culture and transplantation

Effects of Enhanced O2 Transport on Hepatocytes Packed within a Bioartificial Liver Device

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Product

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Effects of Enhanced O₂ Transport on Hepatocytes Packed within a Bioartificial Liver Device