期刊
CELL TRANSPLANTATION
卷 21, 期 8, 页码 1775-1789出版社
SAGE PUBLICATIONS INC
DOI: 10.3727/096368912X640628
关键词
Islet cell clusters (ICCs); Exendin-4; Polyethylene glycol; Transplantation
资金
- World Class University (WCU) program [R31-2008-000-10103]
- Converging Research Center Program [2009-0081879]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) [2010-0027955]
- Ministry of Education, Science and Technology Republic of Korea
Pancreatic islet transplantation is a promising method for curing diabetes mellitus. We proposed in this study a molecularly engineered islet cell clusters (ICCs) that could overcome problems posed by islet transplantation circumstances and host's immune reactions. A gene containing highly releasable exendin-4, an insulinotropic protein, was delivered into single islet cells to enhance glucose sensitivity; thereafter, the cells were reaggregated into small size ICCs. Then the surface of ICCs was modified with biocompatible poly(ethylene glycol)lipid (PEG) (C18) for preventing immune reactions. The regimen of ICCs with low doses of anti-CD154 mAb and tacrolimus could effectively maintain the normal glucose level in diabetic mice. This molecularly engineered PEG-Sp-Ex-4 ICC regimen prevented cell death in transplantation site, partly through improving the regulation of glucose metabolism and by preventing hypoxia- and immune response-induced apoptosis. Application of this remedy is also potentially far-reaching; one would be to help overcome islet supply shortage due to the limited availability of pancreas donors and reduce the immunosuppressant regimens to eliminate their adverse effects.
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