Nano-immunoshielding ising multi-layered hyperbranched polyethylene glycol for the nonhuman primates pancreatic islets xenotransplantation
다층의 하이퍼브렌치형 폴리에틸렌 글리콜로 표면개질한 원숭이 췌장소도의 이종이식
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- Diabetes mellitus; Surface modification; Pancreatic islet transplantation; Poly ethylene glycol; Monkey islet; Nano-immuno shielding
- 학위논문 (석사)-- 서울대학교 대학원 : 약학과, 2015. 2. 변영로.
- Type 1 diabetes mellitus(T1DM) is also known as insulin dependent diabetes mellitus because of genetical autoimmune disease. especially, beta cells are attacked by autoreactive T cells. these days, exogenous insulin therapy is used for this Type 1 diabetes mellitus. However, this therapy can occur many complications such as allergy reaction, hypo and hyper glycemia. To resolve this therapys problems, pancreatic islet transplantation has been in the spotlight.
However, this grafted islet is rejected quickly because of donors immune response. Many immunosuppressive drugs are developed for this rejections, but they also has limitations.
My research introduce the most optimal surface modifications using poly ethylene glycol combinations to increase the survival rate of grafted islet. this technic is called nano-immuno shielding
Poly ethylene glycol is one of biocompatible polymers. they can not induce the immunogenic problems and they can block the protein adsorption and also they are non toxic in human or all kinds of animals body. So if we can coat the islet using this polymer, then this islet can block the adsorption of immune cells or plasma proteins which can work for the initiator of immune response.
In this research, we used non human primates because this species has the most similar morphology compare with human islet.
At first of my research, we fixed the polymer concentrations for getting the minimal toxicity and maximum effectivity. Using several stages, we got the optimal concentrations
0.5% 6-arm PEG NHS, 1% 6-arm PEG DOPA and 0.5% linear PEG SH. Additionally, we made a new immunosuppressive drug protocol. Finally, we treated both immuno shielding and drug protocol and evaluated the islet survival rate and blood glucose.
In this research shows that immuno shielded islet can survive more than 3 times longer compare with intact islet with maintaining the normal blood glucose level. So, using this results, we can make the basic allotransplantation protocols in primates. Also humans islet is similar to the monkey islet, therefore we can predict the result of human allotransplantation.