title: Inhibition of instant blood-mediated inflammatory responses by co-immobilization of sCR1 and heparin on islets.
abstract: Intraportal transplantation of islets of Langerhans is followed by marked islet loss, mainly caused by instant blood-mediated inflammatory responses (IBMIR). We previously developed a method of co-immobilizing sCR1 and heparin on islets. Here we examined whether this process could reduce islet loss following intraportal islet transplantation in a syngeneic mouse model. sCR1-heparin islets or unmodified islet controls were transplanted into the livers of streptozotocin-induced diabetic mice. Transplantation of 100 and 125 sCR1-heparin islets normalized blood glucose levels in 8 of 9 (88.9%) and 9 of 9 diabetic mice (100%), respectively, whereas transplantation of 100 and 125 non-treated islets induced normoglycemia in 0 of 9 and 2 of 9 diabetic mice, respectively. Fibrin staining and plasma insulin measurements indicated that, compared to non-treated islets, sCR1-heparin islet transplantation was associated with fewer blood clots around islets, and significantly less insulin leakage from damaged islets at 1 h post-transplantation. Long-term follow-up of the sCR1-heparin islet group showed islet cells in the livers and insulin expression. In conclusion, co-immobilization of sCR1 and heparin on islets could effectively reduce islet damage by IBMIR, and might be useful to enable transplantation with only one donor and one recipient.
authors.affiliation: Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-Ku, Kyoto, Japan.
authors.forename: Nguyen Minh
authors.initials: NM
authors.lastname: Luan
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology; D005951:Glucose Tolerance Test; D006085:Graft Survival; D006493:Heparin; D055767:Immobilized Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood* / Q000473:pathology*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011951:Receptors, Complement / Q000378:metabolism*; D012995:Solubility; D013997:Time Factors; D014184:Transplantation, Homologous; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D055767:Immobilized Proteins; D007328:Insulin; D011951:Receptors, Complement; D014841:von Willebrand Factor; D006493:Heparin