Barium-cross-linked alginate beads: a simple, one-step method for successful immunoisolated transplantation of islets of Langerhans

Zekorn, T; Hörcher, A; Siebers, U; Schnettler, R.; Klöck, Gerd; Hering, Bernhard J.; Zimmermann, U.; Bretzel, Reinhard G.; Federlin, K.

doi:10.1007/bf00572552

Cited by 65 publications

(50 citation statements)

References 20 publications

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“…Alginate gelification occurs in the presence of divalent cations, such as calcium, barium, and strontium. 21,22,33 Divalent cations interact with blocks of guluronic monomers (G) to form bridges between polymer chains in a highly cooperative fashion. Calcium is widely employed to crosslink alginates, but in some applications barium replaces calcium as it interacts more strongly with G-rich regions and forms a more stable gel.…”

Section: 12mentioning

confidence: 99%

Progress technology in microencapsulation methods for cell therapy

Rabanel

Banquy

Zouaoui

et al. 2009

Biotechnology Progress

122

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Cell encapsulation in microcapsules allows the in situ delivery of secreted proteins to treat different pathological conditions. Spherical microcapsules offer optimal surface-to-volume ratio for protein and nutrient diffusion, and thus, cell viability. This technology permits cell survival along with protein secretion activity upon appropriate host stimuli without the deleterious effects of immunosuppressant drugs. Microcapsules can be classified in 3 categories: matrix-core/shell microcapsules, liquid-core/shell microcapsules, and cells-core/shell microcapsules (or conformal coating). Many preparation techniques using natural or synthetic polymers as well as inorganic compounds have been reported. Matrix-core/shell microcapsules in which cells are hydrogel-embedded, exemplified by alginates capsule, is by far the most studied method. Numerous refinement of the technique have been proposed over the years such as better material characterization and purification, improvements in microbead generation methods, and new microbeads coating techniques. Other approaches, based on liquid-core capsules showed improved protein production and increased cell survival. But aside those more traditional techniques, new techniques are emerging in response to shortcomings of existing methods. More recently, direct cell aggregate coating have been proposed to minimize membrane thickness and implants size. Microcapsule performances are largely dictated by the physicochemical properties of the materials and the preparation techniques employed. Despite numerous promising pre-clinical results, at the present time each methods proposed need further improvements before reaching the clinical phase.

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Section: 12mentioning

confidence: 99%

Progress technology in microencapsulation methods for cell therapy

Rabanel

Banquy

Zouaoui

et al. 2009

Biotechnology Progress

122

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“…[6][7][8][9] Recently, new microcarriers suitable for large-scale cultivation of anchorage-dependent mammalian cells have been developed by coating barium-alginate beads with collagen. 10 Very fragile mammalian cells, plant protoplasts, and tissues (e.g., islets of Langerhans 11,12 and parathyroid tissue 13 ) can be immobilized by entrapping them in alginate gel microspheres, because this procedure is carried out in a single step under very mild conditions. The implementation of this immobilization technique is very simple.…”

Section: Introductionmentioning

confidence: 99%

Dielectric properties of alginate beads and bound water relaxation studied by electrorotation

et al. 1999

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The electrical and dielectric properties of Ba 2ϩ and Ca 2ϩ cross-linked alginate hydrogel beads were studied by means of single-particle electrorotation. The use of microstructured electrodes allowed the measurements to be performed over a wide range of medium conductivity from about 5 mS/m to 1 S/m. Within a conductivity range, the beads exhibited measurable electrorotation response at frequencies above 0.2 MHz with two well-resolved co-and antifield peaks. With increasing medium conductivity, both peaks shifted toward higher frequency and their magnitudes decreased greatly. The results were analyzed using various dielectric models that consider the beads as homogeneous spheres with conductive loss and allow the complex rotational behavior of beads to be explained in terms of conductivity and permittivity of the hydrogel. The rotation spectra could be fitted very accurately by assuming (a) a linear relationship between the internal hydrogel conductivity and the medium conductivity, and (b) a broad internal dispersion of the hydrogel centered between 20 and 40 MHz. We attribute this dispersion to the relaxation of water bound to the polysaccharide matrix of the beads. The dielectric characterization of alginate hydrogels is of enormous interest for biotechnology and medicine, where alginate beads are widely used for immobilization of cells and enzymes, for drug delivery, and as microcarriers for cell cultivation.

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“…2,7,8,10 Alternate types of microcapsules using higher alginate concentrations, different crosslinking reagents, omitting the poly-L-lysine and second alginate layers, or omitting core solubilization, also have been used in vivo. 4,14,15 These capsules were formulated to improve the mechanical stability without compromising the immunoprotective properties.…”

Section: Introductionmentioning

confidence: 99%

Encapsulation of various recombinant mammalian cell types in different alginate microcapsules

Peirone

Ross

Hortelano

et al. 1998

J. Biomed. Mater. Res.

110

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Microencapsulation of recombinant "universal" cells with immunoprotective membranes is an alternate approach to somatic gene therapy. Therapeutic gene products secreted by these cells can be delivered to different patients without immunosuppression or genetic modification of the host's cells. The encapsulation of different mammalian cell types (epithelial cells, fibroblasts, and myoblasts) is compared among three alginate-based microcapsules: (1) calcium-linked alginate microcapsules with a solubilized core and a poly-L-lysine-alginate-laminated surface; (2) barium-linked alginate beads with a gelled core; and (3) a hybrid formulation of barium-linked alginate beads with a poly-L-lysine-alginate-laminated surface. The mechanical stability of the different microcapsule types, as measured with a cone-and-plate shearing apparatus, was superior in the two barium-linked alginate beads. All cell types maintained high viability (65-90%) in culture after encapsulation. The recombinant gene products secreted by these cells (human growth hormone MW = 22,000, human factor IX MW = 57,000, and murine beta-glucuronidase MW = 300,000) were able to traverse the three microcapsule types at similar rates. Cell numbers within the microcapsules increased twofold to > 20-fold over 4 weeks, depending on the cell type. Epithelial and myoblast cell numbers were not affected by microcapsule formulation; however, fibroblasts proliferated the most in the calcium-linked alginate spheres. These results show that for culturing fibroblasts in a mechanically stable environment the classical calcium-linked microcapsules are adequate. However, where mechanical stability is a more critical requirement, the solid barium-linked gelled beads are more appropriate choices.

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Barium-cross-linked alginate beads: a simple, one-step method for successful immunoisolated transplantation of islets of Langerhans

Cited by 65 publications

References 20 publications

Progress technology in microencapsulation methods for cell therapy

Progress technology in microencapsulation methods for cell therapy

Dielectric properties of alginate beads and bound water relaxation studied by electrorotation

Encapsulation of various recombinant mammalian cell types in different alginate microcapsules

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