2018年6月11日学术讲座:基于水凝胶包装猪胰岛细胞的胰岛素药物传递

讲座时间:611日(周一)下午2

讲座地点:微创楼311
讲座题目:Toward Insulin Delivery with Encapsulated Porcine Islet Cells: Click Hydrogels
         基于水凝胶包装猪胰岛细胞的胰岛素药物传递
讲座人:美国马里兰大学帕克分校化学和生物大分子工程系Nam Sun Wang教授
讲座主要内容:

    An over-reaching goal in this study is to find an alternative method of drug delivery to replace the current practice of repeated insulin injection with needles for countless diabetes. More specifically, this project focuses on cell therapy of diabetes where pig pancreatic islet cells were encapsulated in an alginate gel or other hydrogels, and encapsulated islet cells secrete insulin in response to physiological conditions (such as glucose concentration). Encapsulation and hiding of the pig cells in a hydrogel is necessary to bypass the patient's immune system from recognizing and attacking the introduced foreign donor cells. A bioartificial pancreas for the treatment of Type I diabetes is hampered by the lack of a suitable hydrogel to encapsulate islets of Langerhans and to serve as a protective barrier against the host’s immune system. The traditional gel is alginate ionically linked with divalent cations (typically, Ca2+). Unfortunately, alginate gel is unsuitable because ion exchange with monovalent ions from the surrounding serum degrades alginate gel and exposes donor tissue to the host's immune system.

    In this project, we started by studying the effect of cytotoxins that may be present in alginate on the response of immune cells, mainly by measuring nitric oxide production. We also studied how gamma-interferon excited and how certain drugs suppressed the immune cells. We extended the study to hyaluronic acid gels. We synthesized a novel biocompatible alginate gel and hyaluronic acid gel via the click chemistry, instead of crosslinking with cations. Click chemistry is the Cu (I) catalyzed reaction between an azide and alkyne to form a 1,2,3 triazole ring. We successfully synthesized functionalized alginate and hyaluronic acid with alkyne or azide end groups and characterized the stability and transport properties of covalently crosslinked alginate hydrogels and compared them to their ionically crosslinked counterparts. A murine macrophage cell line RAW 264.7 responded well to the new hydrogel under various simulated inflammatory states (with or without endotoxin, with or without the inflammatory cytokine gamma-interferon). Our preparation protocol minimized the hydrogel's cytotoxicity while maintained insulin production in a rat insulinoma cell line RIN-5F. We demonstrate that primary porcine islets of Langerhans encapsulated in our hydrogel was fully functional and responded well to glucose challenges.

主讲人简介:

    Nam Sun Wang,美国马里兰大学帕克分校化学和生物大分子工程系副教授,美国化学学会、美国化工学会和美国生物工程学会等学术组织会员,获美国National Institute of Science and Technology等多项经费资助,主要从事(1)生药制药和生物炼制上下游过程控制 和(2)药物传递和疾病诊断等方向研究。近些年工作包括:1)梭菌中甘油发酵产丁醇代谢途径解析;2)研究大肠杆菌葡萄糖和乙酸转运蛋白和启动子激活用于异源蛋白生产;3)利用阿拉伯糖启动子自定时启动异源蛋白表达;4)渗透压对动物细胞代谢的影响;5)在眼部疾病中视网膜色素上皮细胞运输小分子 (如离子、水、二氧化碳和乳酸)的作用;6)无宿主免疫反应的猪胰腺胰岛细胞凝胶传递胰岛素;7)在食品包装(如牛奶盒)中检测腐败的封装pH值指示剂研究,8)生物活性化合物(如虫草素)和生物聚合物(如普鲁兰多糖)的生产;9)诱导多能干细胞分化成造血或其它功能细胞。