Islet encapsulation with polyphenol coatings decreases pro-inflammatory chemokine synthesis and T cell trafficking.
Islet encapsulation with polyphenol coatings decreases pro-inflammatory chemokine synthesis and T cell trafficking.
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DOI：
10.1016/j.biomaterials.2017.03.002
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发表时间：
2017-06
期刊：
影响因子：
14
通讯作者：
Tse HM
中科院分区：
文献类型：
--
作者：
Pham-Hua D;Padgett LE;Xue B;Anderson B;Zeiger M;Barra JM;Bethea M;Hunter CS;Kozlovskaya V;Kharlampieva E;Tse HM
1型糖尿病（T1 D）是一种慢性促炎性自身免疫性疾病，由参与胰腺β细胞溶解的胰岛浸润性白细胞组成。胰岛移植是T1 D的一种有希望的治疗方法;然而，由于有限的胰岛可用性、免疫抑制剂的不良反应和移植物存活率下降，临床应用受到限制。胰岛包裹可以提供免疫保护屏障以保护胰岛功能并防止移植后免疫介导的排斥反应。我们以前证明了一种新的细胞保护性纳米膜多层涂层的胰岛封装单宁酸（TA），免疫调节抗氧化剂，和聚（N-乙烯基吡咯烷酮）（PVPON）组成，是有效的抑制在体外免疫反应参与移植排斥反应和保存在体外胰岛功能。然而，（PVPON/TA）在体内维持胰岛功能和逆转糖尿病的能力尚未得到测试。最近的证据表明，氧化还原状态的调节可以影响促炎免疫反应。因此，我们假设移植的（PVPON/TA）包封的胰岛可以恢复糖尿病小鼠的免疫功能，并提供免疫保护屏障。我们的研究结果表明，（PVPON/TA）纳米薄膜涂层可以显着减少体外趋化因子的合成和致糖尿病的T细胞迁移。重要的是，（PVPON/TA）包封的胰岛移植到糖尿病小鼠后恢复了正常。我们的研究结果表明，（PVPON/TA）包封的胰岛可能会抑制免疫反应，提高胰岛移植物接受T1 D患者。
Type 1 Diabetes (T1D) is a chronic pro-inflammatory autoimmune disease consisting of islet-infiltrating leukocytes involved in pancreatic β-cell lysis. One promising treatment for T1D is islet transplantation; however, clinical application is constrained due to limited islet availability, adverse effects of immunosuppressants, and declining graft survival. Islet encapsulation may provide an immunoprotective barrier to preserve islet function and prevent immune-mediated rejection after transplantation. We previously demonstrated that a novel cytoprotective nanothin multilayer coating for islet encapsulation consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), was efficacious in dampening in vitro immune responses involved in transplant rejection and preserving in vitro islet function. However, the ability of (PVPON/TA) to maintain islet function in vivo and reverse diabetes has not been tested. Recent evidence has demonstrated that modulation of redox status can affect pro-inflammatory immune responses. Therefore, we hypothesized that transplanted (PVPON/TA)-encapsulated islets can restore euglycemia to diabetic mice and provide an immunoprotective barrier. Our results demonstrate that (PVPON/TA) nanothin coatings can significantly decrease in vitro chemokine synthesis and diabetogenic T cell migration. Importantly, (PVPON/TA)-encapsulated islets restored euglycemia after transplantation into diabetic mice. Our results demonstrate that (PVPON/TA)-encapsulated islets may suppress immune responses and enhance islet allograft acceptance in patients with T1D.