Open AccessPreimplantation of an Immunoprotective Device Can Lower the Curative Dose of Islets to That of Free Islet Transplantation—Studies in a Rodent Model
Author(s) -
Anne Sörenby,
Makiko KumagaiBraesch,
Amit Sharma,
Kjell Hultenby,
Annika Wernerson,
Annika Tibell
Publication year - 2008
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/tp.0b013e31817efc78
Subject(s) - islet , transplantation , renal capsule , capsule , endocrine system , neovascularization , diabetes mellitus , medicine , andrology , urology , endocrinology , biology , hormone , angiogenesis , botany
Islet graft survival inside macroencapsulation devices is suboptimal. We hypothesized that induction of neovascularization by preimplantation of devices would improve the physiological conditions, thereby lowering the number of islets required for cure. Several rat islets were transplanted to TheraCyte immunoprotective devices implanted subcutaneously in diabetic athymic mice. Cure rates in the groups with preimplanted devices were significantly better than in those with freshly implanted devices (375 islets: 8/8 vs. 1/6, P=0.003; 125 islets: 6/6 vs. 0/7, P=0.001). Morphometric evaluations of the 125 islet groups showed higher fractional and absolute volumes of endocrine tissue in the group with preimplanted devices (P<0.001 and P=0.035, respectively). In the following dose titration study, using preimplanted devices, as low as 50 islets cured diabetic mice (100% cure, n=6). We conclude that preimplantation significantly lowers the curative dose of macroencapsulated islets to levels resembling those of free islets transplanted under the renal capsule.