Alginate coating of islets of Langerhans: in vitro studies on a new method for microencapsulation for immuno-isolated transplantation

Zekorn, T; Siebers, U; Hörcher, A; Schnettler, R.; Zimmermann, U.; Bretzel, Reinhard G.; Federlin, K.

doi:10.1007/bf00572829

Cited by 65 publications

(37 citation statements)

References 11 publications

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“…We cannot fully explain why these simple capsules work so well for islet xenografts. Previous studies have shown that barium cross-linkage provides stronger alginate gels than those found with calcium (23). In addition, the avoidance of PLL is probably helpful because the macrophage activation so often seen with PLL might act synergistically with a xenograft reaction.…”

Section: Discussionmentioning

confidence: 99%

Survival and Maturation of Microencapsulated Porcine Neonatal Pancreatic Cell Clusters Transplanted into Immunocompetent Diabetic Mice

et al. 2003

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Differentiation and maturation of porcine neonatal pancreatic cell clusters (NPCCs) microencapsulated in barium alginate were assessed after transplantation into immunocompetent mice. Microencapsulated NPCCs were transplanted into the peritoneal cavity of streptozocin-induced diabetic B6AF1 mice (n ‫؍‬ 32). The microcapsules were removed at 2, 6, and 20 weeks and examined for cellular overgrowth, insulin content, and insulin secretory responses to glucose and glucose with theophylline. The differentiation, maturation, and proliferation of the ␤-cells in the NPCCs were assessed by immunohistochemistry. Blood glucose levels were normalized in 81% of the animals that received a transplant and remained normal until termination of the experiments at 20 weeks. Hyperglycemic blood glucose levels after explantation of the capsules confirmed the function of the encapsulated NPCCs. Insulin content of the encapsulated NPCCs was increased 10-fold at 20 weeks after transplantation compared with pretransplantation levels. A 3.2-fold increase of the ratio of the ␤-cell area to the total cellular area was observed at 20 weeks, demonstrating the maturation of NPCCs into ␤-cells. A s a result of recent progress (1), there is increased interest in islet transplantation as a potential therapy for type 1 diabetes. However, two major barriers must be overcome before islet transplantation can be provided for more patients: 1) the limited availability of human pancreatic tissue and 2) the need for permanent immunosuppression to prevent graft rejection and autoimmunity (2). Xenogeneic islets from pigs and cows (3-5) have been considered as potential sources of islets for transplantation. Many factors favor the use of pigs: the similar structure of porcine and human insulin, the comparable glucose levels, and that both pigs and humans are omnivores. Islet cells can be isolated in large numbers from adult (6 -9) or neonatal pigs (10,11). However, adult pig islets have proved to be difficult to isolate and tend to fare poorly in tissue culture, which has limited their use. Neonatal pancreatic cell clusters (NPCCs) contain a high proportion of islet precursor cells, can be maintained in culture, and differentiate into ␤-cells after transplantation (11). Naked (10,12) or microencapsulated NPCCs (13) have been shown to restore normoglycemia after transplantation into streptozotocin (STZ)-diabetic nude mice.The concept of a bioartificial pancreas, consisting of islets enclosed within immunobarrier membranes, provides a potential way to overcome the need for immunosuppression. Our group recently developed a promising encapsulation method that uses highly purified alginate cross-linked with BaCl 2 , without a separate permselective barrier, which protects islets against allorejection and autoimmunity (14). The aims of this study were to assess the protective capacity of simple barium-alginate capsules in a xenotransplantation model of NPCCs transplanted into STZ-induced diabetic immunocompetent mice and then to evaluate the growth, maturation, a...

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Section: Discussionmentioning

confidence: 99%

Survival and Maturation of Microencapsulated Porcine Neonatal Pancreatic Cell Clusters Transplanted into Immunocompetent Diabetic Mice

et al. 2003

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“…Alginate is the most commonly used material [119] [120]. Many divalent cations including CaCl 2 and BaCl 2 can produce crosslinking of alginate and the degree of crosslinking varies depending on the cation type [120].…”

Section: Therapeutic Actions Of Cells Encapsulatedmentioning

confidence: 99%

Core–shell designed scaffolds for drug delivery and tissue engineering

2015

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“…In encapsulated cells that are implanted as a therapy for diseases such as Type I Diabetes, transport of nutrients and active components (e.g. insulin) must not be hindered, while that of immuno-system agents must be suppressed [11,12,[18][19][20][21][22]. One way of obtaining such selectivity is by controlling surface porosity, namely, the dimensions of the pores through which transport of the diffusants occurs.…”

Section: Introductionmentioning

confidence: 99%

Controlling surface porosity and release from hydrogels using a colloidal particle coating

Rosenberg

Dan

2010

Journal of Colloid and Interface Science

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Alginate coating of islets of Langerhans: in vitro studies on a new method for microencapsulation for immuno-isolated transplantation

Cited by 65 publications

References 11 publications

Survival and Maturation of Microencapsulated Porcine Neonatal Pancreatic Cell Clusters Transplanted into Immunocompetent Diabetic Mice

Survival and Maturation of Microencapsulated Porcine Neonatal Pancreatic Cell Clusters Transplanted into Immunocompetent Diabetic Mice

Core–shell designed scaffolds for drug delivery and tissue engineering

Controlling surface porosity and release from hydrogels using a colloidal particle coating

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