title: Xenotransplantation of islets enclosed in agarose microcapsule carrying soluble complement receptor 1.
abstract: Strong immunological reactions remain a major barrier to treating diabetic patients using xenogeneic islets. In a previous study, we developed a method for enclosing islets with agarose microbeads carrying soluble complement receptor 1 (sCR1-Mics), a potent complement inhibitor in both classical and alternative complement activation pathways. This is the follow-up in vivo study to evaluate the protective effect of these sCR1-Mics using a xenotransplantation model (rats to mice). ACI/NSIc rat islets enclosed in sCR1-Mics were transplanted into the intraperitoneal cavity of diabetic C57BL/6 mice without immunosuppression therapy. Transplantation of islets in plain agarose microbeads (Mics) was used as a reference. While islets enclosed in plain Mics were rapidly destroyed (graft survival in recipients of 1000 islets: 11.6±3.8 days), transplantation of islets in sCR1-Mics significantly prolonged graft survival (34.1±3.2 days). Moreover, intraperitoneal glucose tolerance tests revealed that islets in sCR1-Mics normalized blood glucose levels in a similar manner as islets in pancreas of normal mice. In conclusion, sCR1 immobilized onto agarose microbeads exerted some protective effect in xenogeneic islets resulting in prolonged graft survival.
authors.affiliation: Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Nguyen Minh
authors.initials: NM
authors.lastname: Luan
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
mesh_terms: D000818:Animals; D016466:CHO Cells; D002214:Capsules; D002478:Cells, Cultured; D006224:Cricetinae; D005951:Glucose Tolerance Test; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011912:Rats, Inbred ACI; D011951:Receptors, Complement / Q000737:chemistry / Q000276:immunology*; D012685:Sepharose / Q000737:chemistry*; D014183:Transplantation, Heterologous
chemical_list: D002214:Capsules; D055767:Immobilized Proteins; D011951:Receptors, Complement; C082885:soluble complement inhibitor 1; D012685:Sepharose