title: Layer-by-layer co-immobilization of soluble complement receptor 1 and heparin on islets.
abstract: Early graft loss due to instant blood-mediated inflammatory reactions (IBMIRs) is a major obstacle of clinical islet transplantation; inhibition of blood coagulation and complement activation is necessary to inhibit IBMIRs. Here, human soluble form complement receptor 1 (sCR1) and heparin were co-immobilized onto the surfaces of islet cells. sCR1 molecules carrying thiol groups were immobilized through maleimide-poly(ethylene glycol)-phospholipids anchored in the lipid bilayers of islet cells. Heparin was immobilized on the sCR1 layer via the affinity between sCR1 and heparin, and additional layers of sCR1 and heparin were formed layer-by-layer. The sCR1 and heparin molecules in these layers maintained anti-complement activation and anti-coagulation activities, respectively. This promising method could be employed to reduce the number of islet cells required to reverse hyperglycemia and prolong graft survival in both allo- and xeno-islet transplantation.
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: Yuji
authors.initials: Y
authors.lastname: Teramura
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011951:Receptors, Complement / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D013499:Surface Properties / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology
chemical_list: D055767:Immobilized Proteins; D007328:Insulin; D020011:Protective Agents; D011951:Receptors, Complement; C082885:soluble complement inhibitor 1; D006493:Heparin; D013917:Thrombin; D005947:Glucose