Lee Dong Yun, Park Sang Jin, Lee Seulki, Nam Jong Hee, Byun Youngro
College of Pharmacy, Seoul National University, Seoul, South Korea.
Tissue Eng. 2007 Aug;13(8):2133-41. doi: 10.1089/ten.2006.0009.
The surface modification of islets using poly(ethylene glycol) (PEG) is being studied as a means of preventing host immune responses against transplanted islets. In this study, to completely shield islets with PEG molecules, we increased the amount of PEG conjugated to islet surfaces, by multiple PEGylation or amplified PEGylation using poly-L-lysine, poly(allylamine), or poly(ethyleneimine), respectively. Amplified PEGylation was associated with islet cytotoxicity and functional impairment, but multiple PEGylation affected neither islet viability nor functionality. In addition, when triply PEGylated islets were allotransplanted into diabetic recipients, these islets survived in 3 of the 7 recipients for more than 100 days without any immunosuppressive treatment. Moreover, the blood glucose levels of these 3 recipients were stable and in the normal range. Immunohistochemical analysis showed that 3 of 7 triply PEGylated islets transplants survived for 100 days and that 4 that were rejected before day 20 were all immunologically protected from immune cells. However, unmodified islets were completely destroyed within 1 week. Consequently, we suggest that multiple PEGylation offers an effective means of reducing the immunogenicity of transplanted islets by increasing the amount of surface-bound PEG.
使用聚乙二醇（PEG）对胰岛进行表面修饰作为一种防止宿主对移植胰岛产生免疫反应的方法正在被研究。在本研究中，为了用PEG分子完全覆盖胰岛，我们分别通过多次聚乙二醇化或使用聚-L-赖氨酸、聚烯丙胺或聚乙烯亚胺进行扩增聚乙二醇化，增加了结合到胰岛表面的PEG量。扩增聚乙二醇化与胰岛细胞毒性和功能损害有关，但多次聚乙二醇化既不影响胰岛活力也不影响其功能。此外，当将三次聚乙二醇化的胰岛同种异体移植到糖尿病受体中时，在7名受体中的3名中，这些胰岛在没有任何免疫抑制治疗的情况下存活了100多天。而且，这3名受体的血糖水平稳定且在正常范围内。免疫组织化学分析表明，7次三次聚乙二醇化胰岛移植中有3次存活了100天，而在第20天之前被排斥的4次移植都在免疫上受到保护免受免疫细胞攻击。然而，未修饰的胰岛在1周内被完全破坏。因此，我们认为多次聚乙二醇化通过增加表面结合的PEG量提供了一种降低移植胰岛免疫原性的有效方法。
