Jang Ji Yeon, Lee Dong Yun, Park Sang Jin, Byun Youngro
Department of Materials Science and Engineering, Kwangju Institute of Science and Technology, 1 Oryong-dong, Puk-gu, Gwangju 500-712, South Korea.
Biomaterials. 2004 Aug;25(17):3663-9. doi: 10.1016/j.biomaterials.2003.10.062.
Graft rejection is the major limiting factor in islet transplantation and is closely related with the recruitment and activation of T cells and macrophages against the graft. To reduce the immunogenicity of islets, we have grafted biocompatible polyethylene glycol (PEG) onto the collagen capsule of islets without changing the morphology and function of islets. In this study, we evaluated whether the grafted PEG molecules on the collagen capsule of islet could prevent the activation of immune cells, and investigated factors that are mainly related to the immune reaction in vitro. During the co-culture with lymphocytes, the morphology and viability of PEG-grafted islets were not damaged, and the amounts of IL-2 and TNF-alpha secreted from lymphocytes co-cultured with PEG-grafted islets were significantly lower than that of free islets. However, when both kinds of islets were cultured with macrophages, there were no significant differences in morphology, viability and the secreted amounts of cytokines and nitric oxide. In conclusion, the grafted PEG could inhibit activation of lymphocytes, which are essential in initiating the graft rejection process. However, the grafted PEG molecules could not completely prevent the infiltration of cytotoxic molecules into the islets.
移植物排斥是胰岛移植的主要限制因素,与针对移植物的T细胞和巨噬细胞的募集及激活密切相关。为降低胰岛的免疫原性,我们已将生物相容性聚乙二醇(PEG)接枝到胰岛的胶原胶囊上,而不改变胰岛的形态和功能。在本研究中,我们评估了接枝在胰岛胶原胶囊上的PEG分子是否能阻止免疫细胞的激活,并研究了体外主要与免疫反应相关的因素。在与淋巴细胞共培养期间,PEG接枝胰岛的形态和活力未受损,与PEG接枝胰岛共培养的淋巴细胞分泌的IL-2和TNF-α量显著低于游离胰岛。然而,当两种胰岛与巨噬细胞一起培养时,在形态、活力以及细胞因子和一氧化氮的分泌量方面没有显著差异。总之,接枝的PEG可抑制淋巴细胞的激活,而淋巴细胞的激活在启动移植物排斥过程中至关重要。然而,接枝的PEG分子不能完全阻止细胞毒性分子渗入胰岛。