Formation of porcine hepatocyte spheroids for use in a bioartificial liver

Liver failure, notwithstanding advances in medical management, remains a cause of considerable morbidity and mortality in the developed world. Although bioartificial liver (BAL) support systems offer the potential of significant therapeutic benefit for such patients, many issues relating to their use are still to be resolved. In this review, these issues are examined in terms of the functions required, the cells of choice in such a system, and the most appropriate environment to optimize the function of such cells T he development of nonbiological systems to support critically ill patients with acute liver failure (ALF) that incorporate plasmapheresis, 1 charcoal hemoperfusion, 2 and ultrafiltration techniques 3 has not had a significant impact on survival. Consequently, hepatocytebased biological systems have attracted intense interest worldwide but have also generated most of the controversy. Uncertainty exists about the most suitable biological component and the risk for zoonoses and immune rejection in the host. In addition, the optimization of culture conditions and thus metabolic function of the biological component have not been systematically studied, although continuing improvements in these areas have rendered this therapeutic avenue in ALF more promising. To compound matters, the question of which aspects of hepatocyte metabolism in an artificial liver are required to sustain life and promote recovery remains largely unanswered, further limiting development. In this review, the biological substrate of such systems is critically examined and insights are provided into the ideal system.

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“…Again, such modalities are at an experimental stage, and their applicability remains to be confirmed. [67][68][69][70][71][72] …”

Section: Novel Culture Modalitiesmentioning

confidence: 99%

Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

Tsiaoussis

Newsome

Nelson

et al. 2001

Liver Transplantation

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“…In addition, we wanted to culture hepatocytes as small aggregates, known to maintain many of the cytoarchitectural characteristics found in vivo and to exhibit higher and more prolonged functional activity than hepatocytes cultured in monolayers (25)(26)(27). Special attention was paid to optimal oxygenation of the cells, since oxygen plays an important role in hepatocyte attachment (28) and function (29,30).…”

mentioning

confidence: 99%

In vitro evaluation of a novel bioreactor based on an integral oxygenator and a spirally wound nonwoven polyester matrix for hepatocyte culture as small aggregates

Flendrig

Soe

Jörning

et al. 1997

Journal of Hepatology

229

140

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“…Large aggregates of about 2-5 mm formed a shell of glycogen-positive viable cells circumscribing a core of eosinophilic cells, the latter observation, probably due to perturbed mass transport, and O 2 diffusion limitations. These spheroidal aggregates formed consistently and rapidly within 12-24 h. This contrasts with the 5-day culture period required to form hepatic spheroid cultures using spinner flasks or in ECM-hepatocyte growth factor (HGF) microarrays in unit gravity [Lazar et al, 1995b;Abu-Absi et al, 2002;Jones et al, 2009].…”

Section: Discussionmentioning

confidence: 64%

Low-Shear Modelled Microgravity Environment Maintains Morphology and Differentiated Functionality of Primary Porcine Hepatocyte Cultures

Nelson

Walker

Hayes

et al. 2010

Cells Tissues Organs

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ity and differentiated functionality, including expression of hepatic integrin ␣ 5 , as markers of functional morphology. We report here that in the absence of exogenous biomatrix scaffolding, hepatocytes cultured in serum-free chemically defined medium in a microgravity environment rapidly ( ! 24 h) Key WordsDifferentiation ؒ Integrin ؒ Microgravity ؒ Morphology, functional ؒ Ultrastructure/electron microscopy ؒ Low fluid shear ؒ Polarity ؒ Three-dimensional liver cultures ؒ Three-dimensional hepatocyte culture Abstract Hepatocytes cultured in conventional static culture rapidly lose polarity and differentiated function. This could be explained by gravity-induced sedimentation, which prevents formation of complete three-dimensional (3D) cell-cell/cellmatrix interactions and disrupts integrin-mediated signals (including the most abundant hepatic integrin ␣ 5 ␤ 1 ), important for cellular polarity and differentiation. Cell culture in a low fluid shear modelled microgravity (about 10 -2 g ) environment promotes spatial colocation/self-aggregation of dissociated cells and induction of 3D differentiated liver morphology. Previously, we demonstrated the utility of a NASA rotary bioreactor in maintaining key metabolic functions and 3D aggregate formation of high-density primary porcine hepatocyte cultures over 21 days. Using serum-free chemically defined medium, without confounding interactions of exogenous bioscaffolding or bioenhancing surface materials, we investigated features of hepatic cellular polar-

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Formation of porcine hepatocyte spheroids for use in a bioartificial liver

Cited by 69 publications

References 19 publications

Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

In vitro evaluation of a novel bioreactor based on an integral oxygenator and a spirally wound nonwoven polyester matrix for hepatocyte culture as small aggregates

Low-Shear Modelled Microgravity Environment Maintains Morphology and Differentiated Functionality of Primary Porcine Hepatocyte Cultures

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