title: Benefits of PEGylation in the early post-transplant period of intraportal islet transplantation as assessed by magnetic resonance imaging of labeled islets.
abstract: While a few studies have demonstrated the benefit of PEGylation in islet transplantation, most have employed renal subcapsular models and none have performed direct comparisons of islet mass in intraportal islet transplantation using islet magnetic resonance imaging (MRI). In this study, our aim was to demonstrate the benefit of PEGylation in the early post-transplant period of intraportal islet transplantation with a novel algorithm for islet MRI. Islets were PEGylated after ferucarbotran labeling in a rat syngeneic intraportal islet transplantation model followed by comparisons of post-transplant glycemic levels in recipient rats infused with PEGylated (n = 12) and non-PEGylated (n = 13) islets. The total area of hypointense spots and the number of hypointense spots larger than 1.758 mm(2) of PEGylated and non-PEGylated islets were quantitatively compared. The total area of hypointense spots (P < 0.05) and the number of hypointense spots larger than 1.758 mm(2) (P < 0.05) were higher in the PEGylated islet group 7 and 14 days post translation (DPT). These results translated into better post-transplant outcomes in the PEGylated islet group 28 DPT. In validation experiments, MRI parameters obtained 1, 7, and 14 DPT predicted normoglycemia 4 wk post-transplantation. We directly demonstrated the benefit of islet PEGylation in protection against nonspecific islet destruction in the early post-transplant period of intraportal islet transplantation using a novel algorithm for islet MRI. This novel algorithm could serve as a useful tool to demonstrate such benefit in future clinical trials of islet transplantation using PEGylated islets.
authors.affiliation: a Division of Endocrinology and Metabolism; Department of Medicine; Samsung Medical Center; Sungkyunkwan University School of Medicine; Seoul, Republic of Korea.
authors.forename: Sang-Man
authors.initials: SM
authors.lastname: Jin
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Oh
authors.forename: Bae Jun
authors.initials: BJ
authors.lastname: Oh
authors.forename: Sunghwan
authors.initials: S
authors.lastname: Suh
authors.forename: Ji Cheol
authors.initials: JC
authors.lastname: Bae
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
authors.forename: Moon-Kyu
authors.initials: MK
authors.lastname: Lee
authors.forename: Kwang-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000601:surgery; D006085:Graft Survival / Q000187:drug effects; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011169:Portal Vein; D051381:Rats; D011917:Rats, Inbred Lew; D013194:Staining and Labeling; D013311:Streptozocin; D013499:Surface Properties / Q000187:drug effects; D014185:Transplantation, Isogeneic
chemical_list: D011092:Polyethylene Glycols; D013311:Streptozocin
keywords: PEGylation; intraportal; islet transplantation; magnetic resonance imaging; superparamagnetic iron oxide nanoparticles