title: Antifibrotic effect of rapamycin containing polyethylene glycol-coated alginate microcapsule in islet xenotransplantation.
abstract: Islet microencapsulation is an attractive strategy for the minimization or avoidance of life-long immunosuppression after transplantation. However, the clinical implementation of this technique is currently limited by incomplete biocompatibility. Thus, the aim of the present study was to demonstrate the improved biocompatibility of rapamycin-containing polyethylene glycol (Rapa-PEG)-coating on alginate microcapsules containing xenogeneic islets. The Rapa-PEG-coating on the alginate layer was observed using scanning electron microscopy (SEM) and the molecular cut-off weight of the microcapsules was approximately 70 kDa. The viabilities of the alginate-encapsulated and Rapa-PEG-coated alginate-encapsulated islets were lower than the viability of the naked islets just after encapsulation, but these the differences diminished over time in culture dishes. Rapa-PEG-coating on the alginate capsules effectively decreased the proliferation of macrophage cells compared to the non-coating and alginate coating of xenogeneic pancreas tissues. Glucose-stimulated insulin secretion did not significantly differ among the groups prior to transplantation. The random blood glucose levels of diabetic mice significantly improved following the transplantation of alginate-encapsulated and Rapa-PEG-coated alginate-encapsulated islets, but there were no significant differences between these two groups. However, there was a significant decrease in the number of microcapsules with fibrotic cell infiltration in the Rapa-PEG-coated alginate microcapsule group compared to the alginate microcapsule group. In conclusion, Rapa-PEG-coating might be an effective technique with which to improve the biocompatibility of microcapsules containing xenogeneic islets. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Heon-Seok
authors.initials: HS
authors.lastname: Park
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.|Convergent Research Consortium for Immunologic Disease, Seoul St Mary's Hospital, Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hae Kyung
authors.initials: HK
authors.lastname: Yang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Dong-Sik
authors.initials: DS
authors.lastname: Ham
authors.affiliation: Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Cheng-Lin
authors.initials: CL
authors.lastname: Sun
authors.affiliation: Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Hong
authors.affiliation: Department of Polymer Nano Science and Technology, Department of BIN Fusion Technology and BK-21 Polymer BIN Fusion Research Team, Chonbuk National University, Dukjin, Jeonju, Republic of Korea.
authors.forename: Gilson
authors.initials: G
authors.lastname: Khang
authors.affiliation: Department of Microbiology and Immunology, Translational Xenotransplantation Research Centre, Cancer Research Institute, Biomedical Research Institute, College of Medicine, Seoul National University, Republic of Korea.
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.|Convergent Research Consortium for Immunologic Disease, Seoul St Mary's Hospital, Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Yoon
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology; D005355:Fibrosis; D005947:Glucose / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D020123:Sirolimus / Q000494:pharmacology*; D034421:Sus scrofa; D014183:Transplantation, Heterologous
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D001786:Blood Glucose; D002214:Capsules; D020099:Coated Materials, Biocompatible; D006603:Hexuronic Acids; D007328:Insulin; D011092:Polyethylene Glycols; D020723:Glucuronic Acid; D005947:Glucose; D020123:Sirolimus
keywords: biocompatibility; diabetes mellitus; fibrosis infiltration; islet transplantation; microcapsule; rapamycin