Biocompatibility of mannuronic acid-rich alginates

Klöck, Gerd; Pfeffermann, Anja; Ryser, Christoph; Gröhn, Patrik; Kuttler, Beate; Hahn, Hans-Jürgen; Zimmermann, U.

doi:10.1016/s0142-9612(96)00204-9

Cited by 291 publications

(163 citation statements)

References 26 publications

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“…These capsules are stable and highly biocompatible in NOD and BALB/c mice, consistent with a previous finding that high-M alginates are as biocompatible as high-G alginates (24). In addition, the high purity of the alginate and the reduction in endotoxin levels probably accounted for much of our success.…”

Section: Discussionsupporting

confidence: 90%

Complete Protection of Islets Against Allorejection and Autoimmunity by a Simple Barium-Alginate Membrane

Duvivier‐Kali

Omer²,

Parent³

et al. 2001

Diabetes

263

199

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We describe a new technique for microencapsulation with high-mannuronic acid (high-M) alginate crosslinked with BaCl 2 without a traditional permselective component, which allows the production of biocompatible capsules that allow prolonged survival of syngeneic and allogeneic transplanted islets in diabetic BALB/c and NOD mice for >350 days. The normalization of the glycemia in the transplanted mice was associated with normal glucose profiles in response to intravenous glucose tolerance tests. After explantation of the capsules, all mice became hyperglycemic, demonstrating the efficacy of the encapsulated islets. The retrieved capsules were free of cellular overgrowth and islets responded to glucose stimulation with a 5-to 10-fold increase of insulin secretion. Transfer of splenocytes isolated from transplanted NOD mice to NOD/SCID mice adoptively transferred diabetes, indicating that NOD recipients maintained islet-specific autoimmunity. In conclusion, we have developed a simple technique for microencapsulation that prolongs islet survival without immunosuppression, providing complete protection against allorejection and the recurrence of autoimmune diabetes. Diabetes 50: 1698 -1705, 2001 I slet transplantation represents an important alternative for the treatment of type 1 diabetes but still requires immunosuppressive agents with their serious side effects (1). One approach to avoid such treatment is to protect islets from the host's immune system with a semipermeable, biocompatible membrane (2,3). Transplantation of islets contained in alginate-poly-L-lysine (PLL) capsules was first described by Lim and Sun (4). Numerous studies have shown successful reversal of diabetes by transplantation of islets enclosed in alginate-PLL capsules in streptozotocin-induced animals (5-9). However, limited success has been reported in spontaneously diabetic NOD mice, a model of autoimmune diabetes (10 -13). Various factors have been implicated in the failure of encapsulated islets. A cellular reaction surrounding the capsules has often been observed, which could lead to depletion of oxygen and nutrients (14) or production of toxic cytokines (15). This accumulation of cells could be due to an immune response to the contained islets or to bioincompatibility of the capsular materials (16,17). Failure might also be attributed to problems with ␤-cell viability in the capsules (18).Protection of porcine islets remains a goal of encapsulation, but xenografts might be more difficult to protect than allografts, as suggested by studies performed with permeable polymer membranes (19,20). This concept is important because of the improved prospects for obtaining an abundant supply of human ␤-cells from precursor cells (21,22). The goal of this study was to determine whether stable biocompatible alginate microcapsules without a permselective component, such as PLL or polyethylene-glycol, would be able to protect mouse islets against allorejection and autoimmunity. RESEARCH DESIGN AND METHODSIslet isolation. Islets were isolated from ma...

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Section: Discussionsupporting

confidence: 90%

Complete Protection of Islets Against Allorejection and Autoimmunity by a Simple Barium-Alginate Membrane

Duvivier‐Kali

Omer²,

Parent³

et al. 2001

Diabetes

263

199

View full text Add to dashboard Cite

show abstract

“…Alginate, a polysaccharide extracted from seaweed for use in the food industry and healthcare, has been shown to be contaminated with endotoxin (10,11). This finding is in line with the results of our study, in which endotoxin was found in fresh seaweed.…”

Section: Discussionsupporting

confidence: 92%

Acute effects after occupational endotoxin exposure at a spa

Holm

Johannesson²,

Torén³

et al. 2009

Scand J Work Environ Health

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“…Up to now the success rates of transplantation of microencapsulated islets were low [5,[24][25][26][27]. This is Table 2 Elemental surface composition of Ca-beads (n ¼ 4) and alginate-PLL capsules (n ¼ 4) before implantation and an analysis of pure PLL (representative sample is shown) mainly caused by insufficient biocompatibility of the applied capsule materials [5,[28][29][30] which induced a non-specific foreign body reaction against not only a small portion but against the whole capsule graft with fibrosis of the capsules and necrosis of the islets as a consequence.…”

Section: Discussionmentioning

confidence: 99%