Tianjin Key Laboratory of Biomedical Materials, Biomedical Barriers Research Center, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China.
Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Yunnan 650101, China.
Biomater Sci. 2023 Feb 14;11(4):1470-1485. doi: 10.1039/d2bm01009g.
Pancreatic islet surface engineering has been proposed as an "easy-to-adopt" approach to enhance post-transplantation islet engraftment for treatment against diabetes. Inulin is an FDA-approved dietary prebiotic with reported anti-diabetic, anti-inflammatory, anti-hypoxic and pro-angiogenic properties. We therefore assessed whether inulin would be a viable option for islet surface engineering. Inulin was oxidized to generate inulin-CHO, which would bind to the cell membrane covalent bond formation between -CHO and -NH across the islet cell membrane. assessments demonstrated enhanced islet viability and better glucose-induced insulin secretion from inulin-coated (5 mg mL) islets, which was accompanied by enhanced revascularization, shown as significantly enhanced tube formation and branching of islet endothelial MS1 cells following co-culture with inulin-coated islets. Reduction of cytokine-induced cell death was also observed from inulin-coated islets following exposure to pro-inflammatory cytokine LPS. LPS-induced ROS production was significantly dampened by 44% in inulin-coated islets when compared to controls. RNA-seq analysis of inulin-coated and control islets identified expression alterations of genes involved in islet function, vascular formation and immune regulation, supporting the positive impact of inulin on islet preservation. examination using streptozotocin (STZ)-induced hyperglycemic mice further showed moderately better maintained plasma glucose levels in mice received transplantation of inulin-coated islets, attributable to ameliorated CD45 immune cell infiltration and improved graft vascularization. We therefore propose islet surface engineering with inulin as safe and beneficial, and further assessment is required to verify its applicability in clinical islet transplantation.
胰岛表面工程被提议作为一种“易于采用”的方法,以增强移植后胰岛的植入,用于治疗糖尿病。菊粉是一种经 FDA 批准的膳食益生元,具有抗糖尿病、抗炎、抗缺氧和促血管生成的特性。因此,我们评估了菊粉是否是胰岛表面工程的可行选择。菊粉被氧化生成菊粉-CHO,它将通过胰岛细胞膜上的-CHO 和 -NH 之间的共价键形成与细胞膜结合。评估表明,包被有菊粉(5mg/mL)的胰岛具有更高的胰岛活力和更好的葡萄糖诱导的胰岛素分泌功能,同时伴随着更好的血管再生,表现为与包被有菊粉的胰岛共培养后胰岛内皮 MS1 细胞的管形成和分支明显增强。还观察到包被有菊粉的胰岛在暴露于促炎细胞因子 LPS 后,细胞因子诱导的细胞死亡减少。与对照组相比,包被有菊粉的胰岛中 LPS 诱导的 ROS 产生减少了 44%。对包被有菊粉和对照胰岛的 RNA-seq 分析鉴定出与胰岛功能、血管形成和免疫调节相关的基因表达改变,这支持了菊粉对胰岛保存的积极影响。使用链脲佐菌素(STZ)诱导的高血糖小鼠的进一步检查表明,接受包被有菊粉的胰岛移植的小鼠的血浆葡萄糖水平得到了适度更好的维持,这归因于 CD45 免疫细胞浸润的减轻和移植物血管化的改善。因此,我们提出用菊粉进行胰岛表面工程是安全和有益的,需要进一步评估以验证其在临床胰岛移植中的适用性。