Immobilization of the soluble domain of human complement receptor 1 on agarose-encapsulated islets for the prevention of complement activation.
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.
Luan
Nguyen Minh
NM
Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-Cho, Shogoin, Sakyo-Ku, Kyoto 606-8507, Japan.
Teramura
Yuji
Y
Iwata
Hiroo
H
D000818:Animals; D016466:CHO Cells; D003167:Complement Activation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D005947:Glucose / Q000378:metabolism; D006241:Haptens / Q000276:immunology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D055767:Immobilized Proteins / Q000737:chemistry* / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011817:Rabbits; D051381:Rats; D011951:Receptors, Complement / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D012685:Sepharose / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism
D006241:Haptens; D055767:Immobilized Proteins; D007328:Insulin; D008081:Liposomes; D011951:Receptors, Complement; D013438:Sulfhydryl Compounds; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D012685:Sepharose; D005947:Glucose