Enhancing the functional output of transplanted islets in diabetic mice using a drug-eluting scaffold.
Enhancing the functional output of transplanted islets in diabetic mice using a drug-eluting scaffold.
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DOI：
10.1186/s13036-018-0098-3
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发表时间：
2018
影响因子：
5.6
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Zhu K;Dong L;Wang J;Li D;Chen M;Jiang C;Wang J
胰岛移植越来越多地用于糖尿病患者的血糖控制。然而，由于局部炎症、胰岛丢失等原因，移植胰岛的功能输出仍然受到阻碍。为此，在本研究中，我们探索了通过使用含有白细胞介素4 （IL-4）的药物洗脱支架来增强糖尿病小鼠移植胰岛的功能输出。体外研究表明，该支架无细胞毒性，IL-4在一周内快速释放，IL-4保持其生物活性。在胰岛移植后4周的时间窗内，体内研究显示，药物洗脱支架组糖尿病小鼠血液胰岛素和c肽2水平从第2周开始显著升高，有效降低血糖水平。此外，这些小鼠表现出更强的承受快速葡萄糖峰值的能力，这一点可以从突然口服葡萄糖刺激试验结果中得到证明。进一步的机制研究表明，功能输出的增强可能归因于巨噬细胞的M2极化，如胰岛组织中CD163+/CD68+巨噬细胞的增加。人们普遍认为，巨噬细胞的M2极化对局部组织具有抗炎作用，可加速胰岛移植后局部炎症的消退。本研究为胰岛移植后糖尿病患者高血糖的处理提供了新的思路。
Islet transplantation is increasingly used in the diabetic patients to control the blood glucose level. However, the functional output of transplanted islets remains hampered due to the local inflammation, loss of islets, etc. To that end, in this study we explored to enhance the functional output of transplanted islets in diabetic mice by employing a drug-eluting scaffold with a payload of interleukin 4 (IL-4). According to the in vitro studies, the scaffold showed no cytotoxicity, a rapid release of IL-4 within a week and the IL-4 retained its bioactivity. During the 4-week time window after the islet transplantation, in vivo studies showed that the levels of blood insulin and C-peptide 2 in diabetic mice in the drug-eluting scaffold group significantly increased since week 2, which effectively reduced the blood glucose level. In addition, these mice demonstrated a stronger capability to withstand a rapid glucose spike as evidenced by the tolerance of sudden oral glucose challenge test result. A further mechanistic study suggested that the enhanced functional output could be attributed to the M2 polarization of macrophages as evidenced by the increase of CD163+/CD68+ macrophages in the islet tissues. A M2 polarization of macrophages is widely believed to exert an anti-inflammatory influence on local tissues, which could accelerate the resolution of local inflammation following the islet transplantation. Our study shed a new light on the hyperglycemia management of diabetic patients following the islet transplantation.
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