Evaluation of a Hybrid Artificial Liver Using a Polyurethane Foam Packed-Bed Culture System in Dogs

Gion, Tomonobu; Shimada, Mitsuo; Shirabe, Ken; Nakazawa, Kimitaka; Ijima, Hiroyuki; Matsushita, Taku; Funatsu, Kazumori; Sugimachi, Keizō

doi:10.1006/jsre.1998.5540

Cited by 46 publications

(13 citation statements)

References 22 publications

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“…Moreover, the cells in such systems are typically exposed to higher shear forces. Contrastingly, perfused beds=scaffold designs offer an answer to the transport barrier limitations of encapsulation chambers, 7-10 yet unfortunately encounter nonuniform perfusion profiles and clogging of membrane pores, and can expose the cells to shear forces. The flat-plate design is one of the more extensively developed designs.…”

mentioning

confidence: 99%

The Effectiveness of a Novel Cartridge-Based Bioreactor Design in Supporting Liver Cells

Niu

Hammond

Coger

2009

Tissue Engineering Part A

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There are a number of applications-ranging from temporary strategies for organ failure to pharmaceutical testing-that rely on effective bioreactor designs. The significance of these devices is that they provide an environment for maintaining cells in a way that allows them to perform key cellular and tissue functions. In the current study, a novel cartridge-based bioreactor was developed and evaluated. Its unique features include its capacity for cell support and the adaptable design of its cellular space. Specifically, it is able to accommodate functional and reasonably sized tissue (>2.0Â10 8 cells), and can be easily modified to support a range of anchorage-dependent cells. To evaluate its efficacy, it was applied to liver support in the current study. This involved evaluating the performance of rat primary hepatocytes within the unique cartridges in culture-sans bioreactor-and after being loaded within the novel bioreactor. Compared to collagen sandwich culture functional controls, hepatocytes within the unique cartridge design demonstrated significantly higher albumin production and urea secretion rates when cultured under dynamic flow conditions-reaching peak values of 170 AE 22 mg=10 6 cells=day and 195 AE 18 mg=10 6 cells=day, respectively. The bioreactor's effectiveness in supporting live and functioning primary hepatocytes is also presented. Cell viability at the end of 15 days of culture in the new bioreactor was 84 AE 18%, suggesting that the new design is effective in maintaining primary hepatocytes for at least 2 weeks in culture. Liver-specific functions of urea secretion, albumin synthesis, and cytochrome P450 activity were also assessed. The results indicate that hepatocytes are able to achieve good functional performance when cultured within the novel bioreactor. This is especially true in the case of cytochrome P450 activity, where by day 15 of culture, hepatocytes within the bioreactor reached values that were 56.6% higher than achieved by the collagen sandwich functional control cultures. The success of the novel cartridge-based bioreactor in supporting hepatocytes with good viability and functional performance suggests that it is an effective design for supporting anchorage-dependent cells.

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confidence: 99%

The Effectiveness of a Novel Cartridge-Based Bioreactor Design in Supporting Liver Cells

Niu

Hammond

Coger

2009

Tissue Engineering Part A

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“…[74][75][76] Packed bed reactors offer improved mass transfer by allowing direct contact of cells on microcarriers or packing material with the perfusing media. 36,[77][78][79] Another aspect of current BAL designs is the universal absence of functional biliary excretion into an isolated compartment. In current configurations, even primary hepatocytes that regain polarity in vitro (e.g., spheroids or coculture) excrete biliary constituents into the surrounding fluid, which then recirculate continuously.…”

Section: Bioreactor Designmentioning

confidence: 99%

“…86 A packed bed reactor built around a microchanneled scaffold is an example of one designed explicitly to reduce heterogeneous perfusion and improve the transport characteristics of the devices. 79 Cell Viability and Function. One of the major obstacles to BAL offering long-term treatment is the inability to maintain highly functional hepatocytes in vitro.…”

Section: Bioreactor Designmentioning

confidence: 99%

“…Gel entrapment and use of spheroidal aggregates have been introduced into various membrane-based systems to provide chemical and topological ECM cues or cellcell interaction; however, this introduces an additional diffusion barrier. 65,75,79,[87][88][89] Single cell suspensions, used in some devices because of their desirable transport properties, quickly lose metabolic capacity. 90 Some packed bed designs 77,78 and one hollow fiber device 91 seed cells on microcarriers before device assembly.…”

Section: Bioreactor Designmentioning

confidence: 99%

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Advances in bioartificial liver devices

Allen¹

2001

Hepatology

311

188

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“…Furthermore, we showed that a multicapillary polyureplantation in the Western world (1,5), many patients with FHF can never receive a transplant (4,10) because thane foam packed-bed culture system of hepatocyte spheroids, used as a hybrid artificial liver support system of extrahepatic complications (mainly severe cerebral edema). FHF patients might benefit from temporary liver (PUF-HALSS), was effective for FHF management in animal experiments (9,12,13). support techniques, and such a system might also allow the native liver to regenerate, thus avoiding the need As reported previously, we estimated from the above animal study that the minimum number of porcine hepafor liver transplantation.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of a Larger Version of the Hybrid Artificial Liver Support System Using a Polyurethane Foam/Spheroid Packed-Bed Module in a Warm Ischemic Liver Failure Pig Model for Preclinical Experiments

et al. 2003

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We have reported the usefulness of a polyurethane foam packed-bed culture system of hepatocyte spheroids as a hybrid artificial liver support system (PUF-HALSS). The aim of this study was to evaluate in detail the efficacy in serum parameters regarding the liver function of a larger version of the PUF-HALSS containing 2 × 10 10 porcine hepatocytes for clinical use in warm ischemic liver failure pigs. Warm ischemic liver failure pigs weighing 25 kg were divided into two groups: (1) a control group (n = 3), in which each pig was attached to a PUF-HALSS without hepatocytes, and (2) a HALSS group (n = 3), in which each pig was attached to a PUF-HALSS. In the HALSS group, the increase of blood ammonia was completely suppressed and blood lactate levels were significantly suppressed. The Fisher's ratio was better maintained, and the increase of total bile acid, glycochenodeoxycholic acid, and taurochenodeoxycholic acid was significantly suppressed in the HALSS group. Serum creatinine levels were significantly lower, and blood glucose levels were significantly higher in the HALSS group. Serum levels of tumor necrosis factor-α were not elevated in either group. In conclusion, the larger version of the PUF-HALSS demonstrated many advantages as a liver support system in warm ischemic liver failure pigs.

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Evaluation of a Hybrid Artificial Liver Using a Polyurethane Foam Packed-Bed Culture System in Dogs

Cited by 46 publications

References 22 publications

The Effectiveness of a Novel Cartridge-Based Bioreactor Design in Supporting Liver Cells

The Effectiveness of a Novel Cartridge-Based Bioreactor Design in Supporting Liver Cells

Advances in bioartificial liver devices

Efficacy of a Larger Version of the Hybrid Artificial Liver Support System Using a Polyurethane Foam/Spheroid Packed-Bed Module in a Warm Ischemic Liver Failure Pig Model for Preclinical Experiments

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