Immobilization of the soluble domain of human complement receptor 1 on agarose-encapsulated islets for the prevention of complement activation

Biomaterials. 2010 Dec;31(34):8847-53. doi: 10.1016/j.biomaterials.2010.08.004. Epub 2010 Aug 24.

Abstract

The transplantation of islets of Langerhans has been successfully applied to the treatment of insulin-dependent diabetes. However, a shortage of human donors is the hardest obstacle to overcome. We aimed to develop a bioartificial pancreas that can realize xeno-islet transplantation. The islets were encapsulated in agarose microbeads carrying the soluble domain of human complement receptor 1 (sCR1), which is an effective inhibitor of the classical and alternative complement activation pathways. When naked rat islets were cultured in rabbit serum, large amounts of insulin leaked from the damaged islets over the course of a few days incubation, but no damaged cells were observed among islets in sCR1-agarose microbeads cultured in rabbit serum for 4 days. Although low levels of insulin were detected in the rabbit serum, the insulin did not leak from damaged β-cells, it was physiological insulin secreted by the β-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Complement Activation* / drug effects
  • Cricetinae
  • Cricetulus
  • Glucose / metabolism
  • Haptens / immunology
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Immobilized Proteins / chemistry*
  • Immobilized Proteins / metabolism*
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Liposomes / metabolism
  • Protein Structure, Tertiary
  • Rabbits
  • Rats
  • Receptors, Complement / chemistry*
  • Receptors, Complement / isolation & purification
  • Receptors, Complement / metabolism*
  • Sepharose / chemistry*
  • Sepharose / pharmacology
  • Solubility / drug effects
  • Sulfhydryl Compounds / metabolism

Substances

  • Haptens
  • Immobilized Proteins
  • Insulin
  • Liposomes
  • Receptors, Complement
  • Sulfhydryl Compounds
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Sepharose
  • Glucose