Department of Chemical and Biological Engineering, Graduate School of Sciences and Engineering, Koc University, 34450, Istanbul, Turkey.
Department of Biomedical Sciences and Engineering, Graduate School of Sciences and Engineering, Koc University, 34450, Istanbul, Turkey.
Macromol Biosci. 2018 May;18(5):e1800001. doi: 10.1002/mabi.201800001. Epub 2018 Mar 25.
Pancreatic islet transplantation has emerged as a promising treatment for type-1 diabetes (T1D); however, its clinical application is still limited by the life-long use of immunosuppressive drugs, insufficient number of islets to achieve normoglycemia, and large transplantation volume. This paper reports a unique approach for nanothin coating of insulin secreting beta cell aggregates. The coating is based on hydrophobic and covalent interactions between natural acrylate modified cholesterol bearing pullulan (CHPOA) nanogels and MIN6 beta cell aggregates. Beta cell aggregates are prepared as spheroids through hanging drop method, which is optimized with respect to hanging drop volume and initial number of beta cells. These aggregates, defined as pseudoislets, are coated with sequential layers of nanogels and are evaluated as viable and functional for insulin secretion. Coating experiments are carried out using physiologically compatible medium, where pseudoislets are not brought in contact with toxic prepolymer solutions used in existing approaches. This study offers new opportunities through coating of islets with advanced functional materials under completely physiological conditions for clinical translation of cell transplantation technology. The technique developed here will establish a new paradigm for creating tolerable grafts for other chronic diseases such as anemia, cancer, central nervous system (CNS) diseases.
胰岛移植已成为治疗 1 型糖尿病（T1D）的一种有前途的方法；然而，其临床应用仍然受到终身使用免疫抑制剂、达到正常血糖所需的胰岛数量不足以及移植体积大等因素的限制。本文报道了一种独特的胰岛素分泌β细胞聚集体纳米薄涂层方法。该涂层基于天然丙烯酰化胆固醇修饰支链淀粉（CHPOA）纳米凝胶与 MIN6β细胞聚集体之间的疏水和共价相互作用。β细胞聚集体通过悬滴法制备成球体，通过优化悬滴体积和初始β细胞数量来优化。这些聚集体被定义为拟胰岛，然后用纳米凝胶进行层层包裹，并评估其对胰岛素分泌的活力和功能。涂层实验在生理相容的介质中进行，其中拟胰岛不会接触到现有方法中使用的有毒预聚物溶液。这项研究通过在完全生理条件下用先进的功能材料对胰岛进行涂层，为细胞移植技术的临床转化提供了新的机会。这里开发的技术将为治疗贫血、癌症、中枢神经系统（CNS）疾病等其他慢性疾病创造可耐受的移植物建立一个新的范例。
