MRI of transplanted surface-labeled pancreatic islets with heparinized superparamagnetic iron oxide nanoparticles

• Published in: Biomaterials 2011-12, Vol.32 (35), p.9391-9400
• Main Authors: Jung, Min Jin, Lee, Seung Soo, Hwang, Yong Hwa, Jung, Hae Song, Hwang, Jin Wook, Kim, Min Jun, Yoon, Sangwoo, Lee, Dong Yun
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Conjugation; Dentistry; Dextrans - pharmacology; Diabetes Mellitus - pathology; Diabetes Mellitus - therapy; Heparin - pharmacology; Islet; Islets of Langerhans - drug effects; Islets of Langerhans - pathology; Islets of Langerhans - ultrastructure; Islets of Langerhans Transplantation; Kidney - drug effects; Kidney - pathology; Magnetic Resonance Imaging; Magnetite Nanoparticles; Male; Mice; MRI; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Rats; Rats, Sprague-Dawley; Spin Labels; Staining and Labeling; Superparamagnetic iron oxide (SPIO); Surface Properties - drug effects; Transplantation
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2011.08.070

Abstract Transplantation of insulin-secreting pancreatic islets can provide real-time regulation of blood glucose in patients with type 1 diabetes mellitus. Currently, noninvasive and repetitive monitoring of islet engraftment and function is an emerging and promising modality for successful islet transplantation. Here we report a new technique for highly sensitive in vivo magnetic resonance (MR) imaging of transplanted pancreatic islets. To this end, heparinized superparamagnetic iron oxide (heparin-SPIO) nanoparticle was newly synthesized for chemical conjugation onto islet surface. Compared to typical cellular labeling of Feridex® via random endocytosis, chemical conjugation of heparin-SPIO was stable and improved the hypointensity of transplanted islets due to surface modification of every islet. These heparin-SPIO-conjugated islets showed normal viability and insulin secretion, and were quantified by spin echo T2 -weighted MR imaging with linear correlation depending on transplanted islet mass in vitro and in vivo for 30 days. Also, from the immunohistochemistry, we confirmed the existence of heparin-SPIO and insulin biosynthesis in transplanted islets. However, Feridex-uptake islets showed late glucose responsiveness according to changing glucose concentration although they could normally control the blood glucose levels in diabetic mouse. Thus, we anticipate that this surface labeling with heparin-SPIO can be directly applicable for MR imaging of transplanted islets.