Structure protects them from mechanical stress while ensuring exchanges of nutrients or waste molecules within the surrounding medium

The immuno-isolation provided by alginate encapsulation is undoubtedly the major advantage of this technology when intended for transplantation or tissue regeneration. In the case of type I diabetes, twenty-five years of preclinical studies have recently made possible significant progress in the implantation of encapsulated Langerhans islets in patients. Compared to other biopolymers, the considerable success of alginate used for microencapsulation relies upon the middle conditions required for the gelation process. Alginate salts, such as sodium-alginate, are composed of residues of Dmannuronic acid and L-guluronic acid covalently – linked in homo- or hetero-blocks, and which have a high affinity for divalent or trivalent ions. Calcium ions interact through ionic crosslinking with the carboxylate groups of monosaccharide residues allowing the formation of a three dimensional network between polymeric chains, with limited effects on cell viability. Numerous works described the antiviral activity of algal carbohydrate polymers leading to promising therapeutic applications when used either alone or associated with existing antiviral drugs. These polysaccharides are extracted from the cell walls of red, brown or green algae from which they account for more than 50% of the dry weight. Besides their considerable structural diversity, all of these polymers are negatively charged and, in most cases, present a high sulfation level. Their antiviral activities target a broad spectrum of human pathogens including enveloped viruses such as human immunodeficiency virus, herpes simplex virus, human cytomegalovirus, dengue virus, and non-enveloped viruses, such as hepatitis A virus and human papillomavirus. Based on their safety and low toxicity, marine polysaccharides are interesting solutions for limiting viral infections in clinical contexts. Although experiences using marine polymers as an orally-delivered agent have been described, only a few clinical studies have been conducted so far. The well-known anticoagulant activity of most sulfated polysaccharides, associated with their high molecular weight which is incompatible with free diffusion towards tissues, explains the obstacles to their use as natural compounds in in vivo conditions. Structural modifications by means of chemical or enzymatic processes can be requested to meet clinical constraints. Although alginate antiviral activity is described as low compared to many other marine polysaccharide compounds, we hypothesized that this property could benefit cells entrapped in calciumalginate beads for further use as implanted tissue or organ supply. For this purpose, using a simple extrusion process, we encapsulated human hepatoma-derived cells, a specific cell line which is up to now the most employed cellular model recognized for both its high permissiveness with regard to hepatitis C virus infection and its ability to produce and secrete HCV particles. The aim of this study was thus to investigate the potential protective effect of Ca-alg hydrogel encapsulating hepatic cells against HCV infection. In all cases, no infectious HCVcc particle was produced in the Torin 1 culture medium. More precisely, the non-translocation of the cleavage products RFP-NLS from cytoplasm to the nucleus showed the inability of the HCV to access the entrapped cells or to activate the HCV receptors to enter into cells. However, our previous data suggested HuH-7 cell cultures in Ca-alg beads were a relevant model for HCV infection for two reasons: i) after their encapsulation in Ca-alg beads with optimized alginate composition, isolated HuH-7 cells proliferated and reorganized into multicellular aggregates.

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