title: Long-term allogeneic islet graft survival in prevascularized subcutaneous sites without immunosuppressive treatment.
abstract: Establishment of noninvasive and efficient islet transplantation site together with the avoidance of immunosuppressive drugs for islet engraftment is currently the two major tasks for islet transplantation approach to treat patients with type 1 diabetes. Here, we proposed a method to achieve long-term allogeneic islet graft function without immunosuppression after transplantation in subcutaneous sites. Two agarose rods with basic fibroblast growth factor and heparin were implanted for 1 week in dorsal subcutaneous sites in diabetic rats. After rod removal, 1500 islets were transplanted into the prevascularized pockets. Islets transplanted in prevascularized but not nontreated subcutaneous sites rapidly reverted hyperglycemia in all streptozotocin-induced diabetic rats. In contrast to transient normalization of blood glucose when allogeneic islets were transplanted into liver, allogeneic islets transplanted into this prevascularized subcutaneous site demonstrated long-term graft survival and function in all three rat strain combinations (Fisher 344 to ACI, Lewis to ACI and Fisher 344 to Wistar), evidenced by nonfasting blood glucose level, plasma insulin concentration, intraperitoneal glucose tolerance test and immunohistochemistry. These results indicated that a subcutaneous site prevascularized by this method is potentially a suitable site for successful allogeneic islet transplantation without immunosuppression.
authors.affiliation: Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: N M
authors.initials: NM
authors.lastname: Luan
authors.forename: H
authors.initials: H
authors.lastname: Iwata
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000401:mortality / Q000628:therapy*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D005951:Glucose Tolerance Test; D006085:Graft Survival / Q000502:physiology*; D006493:Heparin / Q000008:administration & dosage*; D007328:Insulin / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male; D018919:Neovascularization, Physiologic; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D040521:Subcutaneous Tissue / Q000098:blood supply* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D016222:Fibroblast Growth Factor 2; D006493:Heparin
keywords: Allotransplantation; diabetes type 1; islet; neovascularization; subcutaneous