用于胰岛表面工程的益生元菊粉纳米涂层,Biomaterials Science

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用于胰岛表面工程的益生元菊粉纳米涂层
Biomaterials Science ( IF 5.8 ) Pub Date : 2022-12-19 , DOI: 10.1039/d2bm01009g
Jianghai Tang ₁ , Xuanjin Chen ₁ , Hang Shi ₁ , Mingming Zhang ₁ , Zhimin Zhou ₁ , Chuangnian Zhang ₁ , Tingyu Ke ₂ , Deling Kong ₃ , Chen Li ₁

Affiliation

胰岛表面工程已被提议作为一种“易于采用”的方法来增强移植后胰岛植入以治疗糖尿病。菊粉是 FDA 批准的膳食益生元，据报道具有抗糖尿病、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，它会通过-CHO 和-NH ₂跨胰岛细胞膜形成共价键结合到细胞膜上。体外评估表明，菊粉涂层 (5 mg mL ^-1) 胰岛，伴随着增强的血运重建，显示为在与菊粉包被的胰岛共培养后，胰岛内皮 MS1 细胞的管形成和分支显着增强。在暴露于促炎细胞因子 LPS 后，菊粉包被的胰岛也观察到细胞因子诱导的细胞死亡减少。与对照组相比，LPS 诱导的 ROS 产生在菊粉包被的胰岛中显着降低了 44%。菊粉包被和对照胰岛的 RNA-seq 分析确定了与胰岛功能、血管形成和免疫调节有关的基因的表达改变，支持菊粉对胰岛保存的积极影响。体内使用链脲佐菌素 (STZ) 诱导的高血糖小鼠进行的检查进一步表明，在接受菊糖包被胰岛移植的小鼠中，血浆葡萄糖水平得到适度更好的维持，这归因于 CD45 + 免疫细胞浸润的改善和体内移植血管^形成的改善。因此，我们建议使用菊糖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。

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Prebiotic inulin nanocoating for pancreatic islet surface engineering

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 via covalent bond formation between –CHO and –NH₂ across the islet cell membrane. In vitro assessments demonstrated enhanced islet viability and better glucose-induced insulin secretion from inulin-coated (5 mg mL⁻¹) 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. In vivo 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 in vivo 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.

更新日期：2022-12-19

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