Impact of alginate type and bead diameter on mass transfers and the metabolic activities of encapsulated C3A cells in bioartificial liver applications

Gautier, A.; Carpentier, B.; Dufresne, M.; Dinh, Q. Vu; Paullier, Patrick; Legallais, Cécile

doi:10.22203/ecm.v021a08

Cited by 71 publications

(44 citation statements)

References 43 publications

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“…Alginate-based hepatocyte encapsulation is a well-studied subject, based on different materials to enhance bead resistance [18], material biocompatibility [11], [14], hepatocyte viability and functions [36], [37], and cell immunoprotection [38]. According to the different studies presented in the literature, several parameters appeared essential to ensure a successful implantation of cells embedded in a biomaterial:…”

Section: Discussionmentioning

confidence: 99%

Impact of Alginate Composition: From Bead Mechanical Properties to Encapsulated HepG2/C3A Cell Activities for In Vivo Implantation

et al. 2013

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Recently, interest has focused on hepatocytes’ implantation to provide end stage liver failure patients with a temporary support until spontaneous recovery or a suitable donor becomes available. To avoid cell damage and use of an immunosuppressive treatment, hepatic cells could be implanted after encapsulation in a porous biomaterial of bead or capsule shape. The aim of this study was to compare the production and the physical properties of the beads, together with some hepatic cell functions, resulting from the use of different material combinations for cell microencapsulation: alginate alone or combined with type I collagen with or without poly-L-lysine and alginate coatings. Collagen and poly-L-lysine increased the bead mechanical resistance but lowered the mass transfer kinetics of vitamin B12. Proliferation of encapsulated HepG2/C3A cells was shown to be improved in alginate-collagen beads. Finally, when the beads were subcutaneously implanted in mice, the inflammatory response was reduced in the case of alginate mixed with collagen. This in vitro and in vivo study clearly outlines, based on a systematic comparison, the necessity of compromising between material physical properties (mechanical stability and porosity) and cell behavior (viability, proliferation, functionalities) to define optima hepatic cell microencapsulation conditions before implantation.

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Section: Discussionmentioning

confidence: 99%

Impact of Alginate Composition: From Bead Mechanical Properties to Encapsulated HepG2/C3A Cell Activities for In Vivo Implantation

et al. 2013

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“…Some methods to characterize the porous structure of the 3D networks have been previously reported, such as mercury intrusion porosimetry [3], nitrogen physisorption [4], and the diffusion kinetics of relevant solutes [5]. Nevertheless, these techniques cannot be applied in the presence of cells, nor do they give information about modifications produced at the cell-biomaterial interface due to cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Determination of pore size distribution at the cell-hydrogel interface

et al. 2011

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BackgroundAnalyses of the pore size distribution in 3D matrices such as the cell-hydrogel interface are very useful when studying changes and modifications produced as a result of cellular growth and proliferation within the matrix, as pore size distribution plays an important role in the signaling and microenvironment stimuli imparted to the cells. However, the majority of the methods for the assessment of the porosity in biomaterials are not suitable to give quantitative information about the textural properties of these nano-interfaces.FindingsHere, we report a methodology for determining pore size distribution at the cell-hydrogel interface, and the depth of the matrix modified by cell growth by entrapped HepG2 cells in microcapsules made of 0.8% and 1.4% w/v alginate. The method is based on the estimation of the shortest distance between two points of the fibril-like network hydrogel structures using image analysis of TEM pictures. Values of pore size distribution determined using the presented method and those obtained by nitrogen physisorption measurements were compared, showing good agreement. A combination of these methodologies and a study of the cell-hydrogel interface at various cell culture times showed that after three days of culture, HepG2 cells growing in hydrogels composed of 0.8% w/v alginate had more coarse of pores at depths up to 40 nm inwards (a phenomenon most notable in the first 20 nm from the interface). This coarsening phenomenon was weakly observed in the case of cells cultured in hydrogels composed of 1.4% w/v alginate.ConclusionsThe method purposed in this paper allows us to obtain information about the radial deformation of the hydrogel matrix due to cell growth, and the consequent modification of the pore size distribution pattern surrounding the cells, which are extremely important for a wide spectrum of biotechnological, pharmaceutical and biomedical applications.

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“…Moreover, it has been shown that large microsphere diameters can offer favorable permeability and maintain cell viability by improving the exchange of nutrients and growth factors (4). Furthermore, Gautier et al (53) also demonstrated that microspheres with a large diameter of 1,000 μ m provided a reliable entrapment process for hepatocytes to be used as a bioartificial liver. Accordingly microspheres with a diameter of 800 μ m were employed in our study.…”

Section: Discussionmentioning

confidence: 99%

A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro

Zhang

Lü

et al. 2016

International Journal of Molecular Medicine

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Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotransformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two-dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases.

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Impact of alginate type and bead diameter on mass transfers and the metabolic activities of encapsulated C3A cells in bioartificial liver applications

Cited by 71 publications

References 43 publications

Impact of Alginate Composition: From Bead Mechanical Properties to Encapsulated HepG2/C3A Cell Activities for In Vivo Implantation

Impact of Alginate Composition: From Bead Mechanical Properties to Encapsulated HepG2/C3A Cell Activities for In Vivo Implantation

Determination of pore size distribution at the cell-hydrogel interface

A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro

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