Agarose for a bioartificial pancreas

Abstract

Islets were encapsulated into 5% concentration agarose microbeads. The effect of microencapsulation on islet allograft survivals was determined using a streptozotocin-induced diabetic (STZ) mouse and a nonobese diabetic (NOD) mouse as recipients. All five STZ BALB/c mice receiving microencapsulated islets (C57BL/6) maintained normoglycemia indefinitely. When NOD mice were used as recipients of the bioartificial pancreas, four of five grafts (islets from C3H/He) functioned for more than 80 d. Two of five NOD mice maintained normoglycemia until animals were sacrificed at 102 and 192 postoperative d. Microbeads made of commercially available agarose can effectively prolong alloislets functioning in the STZ-diabetic mouse and even in the NOD mouse (animal model of human type I diabetes) without the use of any immunosuppressive drug.

Encapsulation technologies in beta cell replacement therapies for Type 1 diabetes

“…In diabetic canine recipients, these devices demonstrated a 50 % success rate in achieving insulin independence for 7-12 week period, demonstrating efficacy in large animal models [49]. Subcutaneously implanted hollow fiber implants demonstrated better glycemic control, minimal fibrotic response and better protection from the immune system when they were manufactured with smooth outer surfaces compared to implants with rough or fenestrated outer surfaces [50][51][52][53]. Prevost et al [54] reported that AN69 hollow fiber implants containing syngeneic islets demonstrated euglycemia for a 10 week period after transplantation into STZ-induced diabetic rats.…”

Encapsulation and Surface Engineering of Pancreatic Islets: Advances and Challenges

“…Microencapsulation can be achieved via the formation of a gel shell around the islets by polymerization of a precursor solution around islet surfaces. Emulsification is one of the microbead formation methods (Iwata et al, 1992;Yang et al, 1994). PEG/Alginate was used for islets microencapsulation through their mixing with two-phase aqueous emulsion.…”

“…In most cases, smooth round surfaces had the lowest fibrosis promoting effect (Zhang et al, 2008). The most commonly applied materials for microencapsulation are alginate (Lim et al, 1980), agarose (Iwata et al, 1992), PEG and poly(hydroxyethylmetacrylate-methyl methacrylate) (Dawson et al, 1987).…”

“…In this approach maleimide-PEG-conjugated phospholipids were used to first modify the cell membrane surface to promote further interactions with PVA derivatives. It is well-known that PEGconjugated phospholipids can be immobilized on the cell membrane through incorporation of the lipid chains into the cell membrane due to their hydrophobic interactions with the lipid bilayers of the membrane (Iwata et al, 1992). Moreover, PEG-phospholipids are more compatible with cells compared to polycations used in the ionic LbL surface modification of islets.…”

Cell encapsules with tunable transport and mechanical properties

“…The efficiency of agarose microcapsules for cell therapy has been demonstrated by both allo-transplantation and xeno-transplantation of pancreatic islets. [8][9][10] The general method for preparing cell-enclosing agarose microcapsules is based on water-in-oil emulsion, which is followed by a reduction in the temperature to allow gellation of the agarose droplets. In general, the agarose droplets are produced by dispersion of agarose aqueous solution-in-oil via mechanical stirring or shaking.…”