NOVEL DIFFUSION TYPE BIOARTIFICIAL ORGAN

新型扩散型生物人工器官

• 批准号: 2827385
• 负责人: TAKASHI MAKI
• 金额: $ 13.05万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-21 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2827385
• 关键词: artificial endocrine pancreas; biomaterial development /preparation; cell transplantation; diffusion; hamsters; laboratory rat; membrane permeability; pancreatic islet transplantation; tissue engineering; transplantation immunology; xenotransplantation

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.

含有活细胞的免疫排除装置（一种生物人工 器官）具有广泛的用途，可治疗多种疾病 由于特定重要代谢功能的丧失。 这些细胞 产生所需的治疗物质并与免疫分离 淋巴细胞和免疫球蛋白通过半透膜通过 仅小分子，例如特定的治疗物质 如氧气、营养物质和代谢物。 作为免疫淋巴细胞和 抗体被膜排除，这是慢性病的必要条件 免疫抑制被消除。 内含的细胞 生物人工器官可以是新鲜分离的细胞，例如胰腺细胞 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将 1) 通过微创手术引入受体，2) 结构稳定，3) 具有生物相容性，4) 完全可回收， 5) 当同种异体或异种细胞时不需要免疫抑制 被使用。 虽然三种类型的免疫排除装置，即 微胶囊、扩散室和血管化装置 广泛研究用于治疗各种代谢疾病，但没有 尚未完全满足上述要求。 我们最近构思了一种新型扩散型生物人工器官 （“超薄袋”）已成功用于试点研究 当加入胰岛时可改善实验性糖尿病 设备内。 我们的扩散袋的创新特点是 胰岛室的厚度（两个胰岛室之间的距离） 膜）被减小到一个大胰岛的大小，这样所有的 袋内的胰岛靠近膜并暴露于 相同程度的供氧。本提案将确定 超薄袋的最佳配置和条件，可最大程度地提高 胰岛素的产生和胰岛的长期存活并确定 超薄生物人工胰腺是否含有异种 胰岛实现高血糖的长期正常化，而无需 免疫抑制。 我们相信，超 薄袋治疗糖尿病将为更广泛的应用铺平道路 该装置用于治疗各种其他疾病的应用以及 从而将对生物医学研究产生长期影响。