세포 이미징을 위한 MRI 헤파린 조영제 나노입자의 개발

Abstract

Pancreatic islet transplantation is promising therapy for type I diabetes mellitus. However, there are many obstacles including limited donor, poor engraftment caused by blood-mediated inflammation, and cellular tracking after islet transplantation. MRI can noninvasively monitor pathological processes and has seen increased efforts to potential as a central tool for cellular imaging. Various MRI contrast agents have been developed for cellular imaging to distinguish between transplanted islets. However, dextran derivative coated SPIO nanoparticles show irregular efficacy and are not commercially available. Therefore, alternative contrast agent which enables stably labeling cells with non-toxic was required. Moreover, in case of islet, the cell labeling using endocytosis method has been showed low efficacy. Thus, an alternative approach of islet labeling is needed. In chapter I, heparin based SPIO nanoparticles (HSPIO) was developed for non-invasive cellular tracking and compared with dextran coated SPIO. In chapter II, the transplantation volume of microencapsulated islets was reduced by magnetic separation of encapsulated islets from empty capsules. In chapter III, stable conjugation of HSPIO onto islet surface for alternative method of endocytosis was evaluated. Finally, in chapter IV, new method to surface modification on porcine islet with HSPIO was introduced. From these, I anticipate my research to contribute to solve obstacles of cellular tracking in islet transplantation.