Kim, Jung-Sik Lim, Jong-Hyung Nam, Hye-Young Lim, Hyun-Ju Shin, Jun-Seop Shin, Jin-Young Ryu, Ju-Hee Kim, Kwangmeyung Kwon, Ick-Chan Jin, Sang-Man Kim, Hang-Rae Kim, Sang-Joon Park, Chung-Gyu 2024-01-20T14:02:14Z 2024-01-20T14:02:14Z 2021-09-05 2012-09-10 0168-3659 https://pubs.kist.re.kr/handle/201004/128874 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 3.4 days 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. (C) 2012 Elsevier B. V. All rights reserved. English ELSEVIER SCIENCE BV BETA-CELL FUNCTION MINIATURE PIGS PANCREAS ANGIOGENESIS MICE VASCULARIZATION PARAMETERS REVERSAL CARRIER MATRIX In situ application of hydrogel-type fibrin-islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation Article 10.1016/j.jconrel.2012.07.018 1 JOURNAL OF CONTROLLED RELEASE, v.162, no.2, pp.382 - 390 JOURNAL OF CONTROLLED RELEASE 162 2 382 390 scie scopus 000310506400015 2-s2.0-84865327127 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article BETA-CELL FUNCTION MINIATURE PIGS PANCREAS ANGIOGENESIS MICE VASCULARIZATION PARAMETERS REVERSAL CARRIER MATRIX Fibrin Porcine islet Subcutaneous islet transplantation Xenotransplantation