MRI 반응성을 지닌 glycyrrhizin-glycol chitosan conjugation 물질로 코팅된 나노산화철입자를 이용한 자기력 유도성 췌장세포 이식기술 및 면역반응 제어

Abstract

Type 1 diabetes is an auto-immune disease caused by the immune T cells which is destroying the β cells that is responsible for the secretion of insulin. This significantly reduces the ability to control blood sugar levels, which is a disease that maintains high blood sugar levels. As a treatment for such diseases, a method of implanting pancreas cells is now in the spotlight. However, the implanted pancreas cells have a low rate of engraftment and immunesuppression agent is necessary for a long period of time, which reduces the function of the β cell and causes a problem with the constancy of glucose in the body. In order to increase the incidence of the implanted cells and protect the cells from immune reactions, the new way to reduce the nuclear protein, High Mobility group box 1(HMGB1) which is a main factor to make auto immune reaction is developed by coating superparamagnetic iron oxide nanoparticles with glycyrrhizin-glycol chitosan and injecting it into inside of pancreas cells to be guided artificially. First of all, we use glycyrrhizin-glycol conjugation as coating agents to coat superparamagnetic nanoparticles(GC-SPIO) in which glycol chitosan is used as backbone to conjugate glycyrrhizin. Before using it, The feasibility was verified that the penetration within the pancreas cells is well achieved and does not indicate toxicity. As a result, there is no side effect. In addition, an on/off system was developed as a way to efficiently inject gc-spio into the pancreas's cells. It also validates its toxicity and functionality about the number of on/off system cycle, allowing it to inject gc-spio into the pancreas cell, far better than the conventional voluntary injection into the pancreas cell. A study of the amount of the emission of hmgb1 nuclear protein from pancreas cells showed that a burst size of hmgb1 nuclear protein in a group in which gc-spio was injected into inside of pancreas cells were reduced by more than 50 % compared to normal islets and islets which uptake bare-spio. This led to the conclusion that the pancreas cells which uptake gc-spio produced less auto-immune responses than the other groups. The tissue test also showed that the largest amount of transplanted materials existed in the middle 1 lobe compared to other lobes. Therefore, a magnet was attached to amiddle 1 lobe during the transplantation of a pancreas cell. Immunehistochemistry and iron oxide dye tests have confirmed that the most significant amount of gc-spio injected pancreas cells were guided into the middle 1 lobe. In addition, magnetic resonance imaging was also able to confirm both qualitative and quantitative results that the greatest amount of the pancreas cells injected with gc-spio were guided to the middle 1 lobe compared to the other liver’s lobes. Therefore, if we develop this technology further, it will be an effective method of transplantation to treat type 1 diabetes.