title: In situ application of hydrogel-type fibrin-islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation.
abstract: Maximum engraftment of transplanted islets is essential for the clinical application of a subcutaneous site. Significant barriers to the current approaches are associated with their low effectiveness, complexity and unproven biosafety. Here, we evaluated and optimized a fibrin-islet composite for effective glycemic control in a subcutaneous site whose environment is highly hypoxic due to low vascularization potential. In the setting of xenogeneic porcine islet transplantation into the subcutaneous space of a diabetic mouse, the in vivo islet functions were greatly affected by the concentrations of fibrinogen and thrombin. The optimized hydrogel-type fibrin remarkably reduced the marginal islet mass to approximately one tenth that of islets without fibrin. This marginal islet mass was comparable to that in the setting of the subcapsular space of the kidney, which is a highly vascularized organ. Highly vascularized structures were generated inside and on the outer surface of the grafts. A hydrogel-type fibrin-islet composite established early diabetic control within an average of 3.4days after the transplantation. In the mechanistic studies, fibrin promoted local angiogenesis, enhanced islet viability and prevented fragmentation of islets into single cells. In conclusion, in situ application of hydrogel-type fibrin-islet composite may be a promising modality in the clinical success of subcutaneous islet transplantation.
authors: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-Ro, Jongno-Gu, Seoul 110-799, South Korea.
authors: Jung-Sik
authors: JS
authors: Kim
authors: Jong-Hyung
authors: JH
authors: Lim
authors: Hye-Young
authors: HY
authors: Nam
authors: Hyun-Ju
authors: HJ
authors: Lim
authors: Jun-Seop
authors: JS
authors: Shin
authors: Jin-Young
authors: JY
authors: Shin
authors: Ju-Hee
authors: JH
authors: Ryu
authors: Kwangmeyung
authors: K
authors: Kim
authors: Ick-Chan
authors: IC
authors: Kwon
authors: Sang-Man
authors: SM
authors: Jin
authors: Hang-Rae
authors: HR
authors: Kim
authors: Sang-Joon
authors: SJ
authors: Kim
authors: Chung-Gyu
authors: CG
authors: Park
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000097:blood / Q000601:surgery; D005337:Fibrin / Q000008:administration & dosage*; D020100:Hydrogels / Q000008:administration & dosage*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013552:Swine; D014183:Transplantation, Heterologous
chemical_list: D001786:Blood Glucose; D020100:Hydrogels; D005337:Fibrin