Kozlovskaya Veronika, Zavgorodnya Oleksandra, Chen Yi, Ellis Kristin, Tse Hubert M, Cui Wanxing, Thompson J Anthony, Kharlampieva Eugenia
Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294 (USA).
Adv Funct Mater. 2012 Aug 21;22(16):3389-3398. doi: 10.1002/adfm.201200138. Epub 2012 Apr 30.
Though transplantation of pancreatic islet cells has emerged as a promising treatment for Type 1 diabetes its clinical application remains limited due to a number of limitations including both pathogenic innate and adaptive immune responses. We report here on a novel type of multifunctional cytoprotective material applied to coat living pancreatic islets. The coating utilizes hydrogen-bonded interactions of a natural polyphenol (tannic acid) with poly(N-vinylpyrrolidone) deposited on the islet surface via non-ionic layer-by-layer assembly. We demonstrate that the coating is conformal over the surface of mammalian islets including those derived from rat, non-human primate (NHP), and human. In contrast to unmodified controls, the coated islets maintain their viability and β-cell functionality for at least 96 hours . We also determine that the coating demonstrates immunomodulatory cytoprotective properties suppressing pro-inflammatory cytokine synthesis in stimulated bone marrow-derived macrophages and diabetogenic BDC-2.5 T cells. The coating material combines high chemical stability under physiologically relevant conditions with capability of suppressing cytokine synthesis, crucial parameters for prolonged islet integrity, viability, and function . Our study offers new opportunities in the area of advanced multifunctional materials to be used for a cell-based transplantation therapy.
尽管胰岛细胞移植已成为治疗1型糖尿病的一种有前景的方法,但其临床应用仍受到限制,原因包括多种因素,如致病性先天性和适应性免疫反应。我们在此报告一种新型的多功能细胞保护材料,用于包裹活的胰岛。该涂层利用天然多酚(单宁酸)与通过非离子层层组装沉积在胰岛表面的聚(N-乙烯基吡咯烷酮)之间的氢键相互作用。我们证明该涂层在包括大鼠、非人灵长类动物(NHP)和人类来源的哺乳动物胰岛表面是保形的。与未修饰的对照相比,包被的胰岛至少在96小时内保持其活力和β细胞功能。我们还确定该涂层具有免疫调节细胞保护特性,可抑制刺激的骨髓来源巨噬细胞和致糖尿病的BDC-2.5 T细胞中促炎细胞因子的合成。该涂层材料在生理相关条件下具有高化学稳定性,并具有抑制细胞因子合成的能力,这是延长胰岛完整性、活力和功能的关键参数。我们的研究为用于基于细胞的移植治疗的先进多功能材料领域提供了新的机会。