In Vivo Efficacy of a Bioartificial Liver in Improving Spontaneous Recovery From Fulminant Hepatic Failure: A Controlled Study in Pigs1

Cuervas-Mons, Valentín; Colás, A.E.; Rivera, José A.; Prados, Elisa

doi:10.1097/00007890-200002150-00005

Cited by 27 publications

(12 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animal survival is usually considered as a definitive index for accessing the effects of a BAL system [44][45][46][47]. In a controlled study, dogs with ischemic liver failure treated with the HepatAssist incorporated with 5!10 9 matrixattached hepatocytes showed significant neurological and biochemical improvements, but life was not prolonged [48,49].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs

Zhang

et al. 2006

Journal of Hepatology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs

Zhang

et al. 2006

Journal of Hepatology

View full text Add to dashboard Cite

“…The extent to which these goals can be achieved is dependent on several variables, including the number of viable and metabolically active hepatocytes in the device. 6 Unfortunately, hepatocyte viability declines over time following isolation, and this decline limits the effectiveness and duration of BAL therapy. Cryopreservation, which allows cells to be used weeks and months after isolation, may also contribute to premature cell death.…”

mentioning

confidence: 99%

Caspase Inhibition Reduces Apoptotic Death of Cryopreserved Porcine Hepatocytes

et al. 2001

View full text Add to dashboard Cite

Cryopreserved porcine hepatocytes are a ready source of metabolic function for use in a bioartificial liver (BAL). However, cryopreservation is associated with a loss of hepatocyte viability. The mechanism of cell death during cryopreservation is incompletely understood, but may involve apoptosis through caspase activation. This study evaluates the cytoprotective effect of a global caspase inhibitor, benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (ZVADfmk) during cryopreservation of porcine hepatocytes. Freshly isolated porcine hepatocytes (viability, 97.4% ؎ 0.9%) were cryopreserved in 60 mol/L ZVAD-fmk (؉ZVAD group) or without ZVAD-fmk (؊ZVAD group) for 24 to 72 hours. Apoptotic and necrotic death were both observed after thawing and after 24 hours of culture. Caspase 3-like activity was significantly reduced by ZVADfmk, and was associated with improved viability and reduced apoptotic death of porcine hepatocytes after cryopreservation. Mitochondrial membrane potential (MMP) was increased in cultures of porcine hepatocytes that were cryopreserved in ZVAD-fmk. These results demonstrate the following: 1) Caspase 3-like protease activation and apoptosis occurs in porcine hepatocytes during cryopreservation; and 2) mitochondrial injury in this process is reduced by caspase inhibition. (HEPATOLOGY 2001;33:1432-1440.)A number of liver-assist devices have been developed, including the extracorporeal use of isolated mammalian hepatocytes to provide metabolic function in a bioartificial liver (BAL). 1,2 Criteria for successful application of a BAL include bridging patients to liver transplantation, reduction of intracranial hypertension and cerebral edema, and avoidance of liver transplantation in cases of reversible hepatic failure. 3-5 To achieve these goals, hepatocytes in the BAL provide metabolic functions to the patient in liver failure. The extent to which these goals can be achieved is dependent on several variables, including the number of viable and metabolically active hepatocytes in the device. 6 Unfortunately, hepatocyte viability declines over time following isolation, and this decline limits the effectiveness and duration of BAL therapy. Cryopreservation, which allows cells to be used weeks and months after isolation, may also contribute to premature cell death. 7,8 Several BAL systems have been designed to maintain hepatocyte viability ex vivo. One such BAL system involves the entrapment of hepatocytes in cylindrical collagen gels located in the fibers of a hollow fiber bioreactor. 9,10 An in vitro model of this BAL system using gel-entrapped hepatocytes has been developed for static culture experimentation, such as the study of mechanisms of hepatocyte death. 11 The in vitro model avoids the expenses of largescale testing, and multiple experiments can be performed simultaneously. Potential immune interactions, present with in vivo models of BAL testing, are also avoided with in vitro testing.Our recent work has shown that cell death of freshly isolated hepatocytes occurs, in part, by apoptosis. 12...

show abstract

“…Despite current emphasis toward bioartificial liver support systems (5,6,(45)(46)(47)(48)(49)(50)(51), plasma purification by adsorbents offers the simplicity of the use of multiple sorbent regimens aimed at the removal of circulating toxic metabolites in general together with those designed for specific toxin removal (e.g., endotoxins and associated cytokines). In this study, membrane plasma separation with online multisorbent treatment of plasma was demonstrated to have beneficial effects in the treatment of Grade III hepatic coma, and the importance of duration and frequency of treatment was demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Multisorbent Plasma Perfusion in Fulminant Hepatic Failure: Effects of Duration and Frequency of Treatment in Rats with Grade III Hepatic Coma

Ryan¹,

Anilkumar²,

Ben-Hamida³

et al. 2001

Artificial Organs

View full text Add to dashboard Cite

Using the model of galactosamine-induced fulminant hepatic failure in the rat, the effects of multisorbent plasma perfusion over Asahi uncoated spherical charcoal, Plasorba (BR-350) resin, and an endotoxin removing adsorbent (polymyxin B-sepharose) were determined in Grade III hepatic coma animals by studying survival as influenced by timing, duration, and frequency of treatment. The effects of treatment on liver cell proliferation and endotoxin removal also were examined. The results demonstrate that duration and frequency of treatment are major contributing factors in the successful application of nonbiological membrane-based multisorbent liver support systems. Examination of the regenerative activity in the liver indicates an enhanced proliferative response following multisorbent plasma perfusion compared with untreated fulminant hepatic failure (FHF) paired controls. Utilizing an endotoxin removal adsorbent alone, a marked reduction in systemic levels of endotoxin in FHF was demonstrated compared with nonperfused FHF paired controls. Despite current emphasis on bioartificial liver support systems, plasma purification by multisorbent systems offers a simple method for the removal of circulating toxic metabolites in general together with specific toxin removal.

show abstract

In Vivo Efficacy of a Bioartificial Liver in Improving Spontaneous Recovery From Fulminant Hepatic Failure: A Controlled Study in Pigs1

Abstract: Bioartificial liver increases survival and allows spontaneous recovery in pigs with fulminant hepatic failure.

Cited by 27 publications

References 18 publications

Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs

Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs

Caspase Inhibition Reduces Apoptotic Death of Cryopreserved Porcine Hepatocytes

Multisorbent Plasma Perfusion in Fulminant Hepatic Failure: Effects of Duration and Frequency of Treatment in Rats with Grade III Hepatic Coma

Contact Info

Product

Resources

About