NOVEL DIFFUSION TYPE BIOARTIFICIAL ORGAN

新型扩散型生物人工器官

• 批准号: 6056614
• 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 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6056614
• 关键词: artificial endocrine pancreas; biomaterial development /preparation; cell transplantation; diffusion; hamsters; laboratory rat; medical implant science; 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斥装置（生物人工 器官）具有广泛的应用，以治疗各种疾病引起的 丧失特定的重要代谢功能。 的细胞 生产所需的治疗物质是从免疫分离 淋巴细胞和免疫球蛋白通过半透膜， 只有小分子如特定的治疗物质 氧气营养物质和代谢物 作为免疫淋巴细胞， 抗体被膜排除在外，需要慢性 免疫抑制被消除。 包含在细胞中的 生物人工器官可以是新鲜分离的细胞， 胰岛和肝细胞，它们取代功能障碍的细胞， 细胞系和基因工程细胞是定制的， 产生所需的分子。 一个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）生物相容，4）完全可回收， 和5）当同种异体或异种细胞 被使用。 虽然三种类型的免疫排斥装置，即。 微胶囊、扩散室和血管化装置，已经被 广泛研究用于治疗各种代谢疾病，没有 尚未完全达到上述要求。 我们最近构思了一种新型扩散型生物人工器官 (an“超薄袋”），成功地用于试验研究， 改善实验性糖尿病时，包括胰岛 在设备内。 我们的扩散袋的创新功能是 胰岛室的厚度（两个之间的距离） 膜）被减少到一个大的胰岛的大小，所以所有的 囊内的胰岛靠近膜并暴露于 同样的氧气供应。本提案将确定 最佳配置和条件的超薄袋最大 胰岛素的产生和胰岛的长期存活， 含异种的超薄型生物人工胰腺 胰岛实现了高血糖症的长期正常化， 免疫抑制 我们相信，成功开发超 薄袋治疗糖尿病将为广泛的治疗铺平道路 该装置用于治疗各种其他疾病的应用， 从而对生物医学研究产生长远的影响。