NOVEL DIFFUSION TYPE BIOARTIFICIAL ORGAN

含有活细胞的免疫排斥装置(生物人工 器官)在治疗各种疾病方面有广泛的应用 由特定的重要代谢功能丧失所致。这些细胞 产生所需的治疗物质是从免疫中分离出来的 淋巴细胞和免疫球蛋白通过半透膜通过 也只有小分子，如特定的治疗物质 作为氧气、营养素和代谢物。作为免疫淋巴细胞和 抗体被膜排除，这是慢性疾病的要求 免疫抑制被消除了。中包含的单元格 生物人造器官可能是新鲜分离的细胞，如胰腺 胰岛和肝细胞取代功能障碍的细胞以及 定制的细胞系和基因工程细胞 产生所需的分子。理想的生物人工器官应该是1) 通过微创手术引入接受者，2) 结构稳定，3)生物兼容，4)完全可回收， 以及5)异基因或异种细胞不需要免疫抑制 都被使用过。虽然有三种免疫排斥装置，即 微囊、扩散室和血管设备已经被 广泛研究各种代谢性疾病的治疗，没有 已完全达到上述要求。 我们最近构思了一种新的扩散型生物人造器官 (“超薄邮袋”)，它被成功地用于一项试点研究 当包含胰岛时可改善实验性糖尿病 在设备内。我们扩散袋的创新特征是 胰岛腔的厚度(两者之间的距离 膜)被缩小到一个大岛的大小，所以所有的 袋子内的胰岛靠近膜，暴露在 相同程度的氧气供应。本提案将决定 超薄纸袋的最优结构和条件 胰岛素的产生和胰岛的长期存活并确定 含异种的超薄生物人工胰腺 胰岛实现高血糖的长期正常化 免疫抑制。我们相信，成功开发的超 用于治疗糖尿病的薄袋将铺平一条宽广的道路 用于治疗各种其他疾病和疾病的装置的应用 从而实现对生物医学研究的长期影响。

The immune exclusion devices containing viable cells (a bioartificial organ ) have broad application to treating a variety of diseases caused by the loss of specific vital metabolic functions. The cells which produce the desired therapeutic substances are separated from immune lymphocytes and immunoglobulins by semipermeable membranes which pass only small molecules such as the specific therapeutic substance as well as oxygen, nutrients and metabolites. As immune lymphocytes and antibodies are excluded by the membrane, the requirement for chronic immunosuppression is eliminated. The cells contained within the bioartificial organ could be freshly isolated cells such as pancreatic islets and hepatocytes which replace dysfunctioning cells as well as cell lines and genetically engineered cells which are custom-made to produce the desired molecules. An ideal bioartificial organ would 1) be introduced into recipients with a minimally invasive procedure, 2) be structurally stable, 3) be biocompatible, 4) be fully retrievable, and 5) require no immunosuppression when allogeneic or xenogeneic cells are used. Although three types of immune exclusion devices, i.e. microcapsules, diffusion chambers and vascularized devices, have been extensively studied for treatment of various metabolic diseases, none has yet fulfilled the above requirements completely. We have recently conceived a novel diffusion-type bioartificial organ (an "ultra-thin pouch") which was successfully used in a pilot study to ameliorate experimental diabetes when pancreatic islets were included within the device. The innovative feature of our diffusion pouch is that the thickness of the islet chamber (distance between the two membranes) is reduced to the size of a large islet, so that all the islets within the pouch are close to the membrane and exposed to the same degree of oxygen supply. The present proposal will determine the optimal configuration and conditions of the ultra-thin pouch for maximal production of insulin and long-term survival of the islets and determine whether the ultra-thin bioartificial pancreas containing xenogeneic islets achieves long-term normalization of hyperglycemia without immunosuppression. We believe that successful development of the ultra- thin pouch for treatment of diabetes will pave a way to a broad application of the device for treatment of various other diseases and thus will achieve a long-term impact on biomedical research.