PLACENTAL CELLS FOR PROTECTION OF IMPLANTED B ISLETS

用于保护植入 B 胰岛的胎盘细胞

• 批准号: 6352407
• 负责人: Constance M John
• 金额: $ 4.93万
• 依托单位: MANDALMED, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-17 至 2001-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6352407
• 关键词: diabetes mellitus therapy; human tissue; laboratory rat; pancreatic islet transplantation; pancreatic islets; placenta; technology /technique development; trophoblast

Current treatment of diabetes mellitus with insulin injections or pump delivery causes wide swings in blood glucose levels that contribute to complications associated with the disease. There is a tremendous need for a treatment that reproduces the instantaneous response of the normal pancreas to changing glucose levels. Human caveric pancreata are available; people are literally dying along with their islets that could be of life-saving use to diabetic patients. Transplantation of beta islets into non- MHC matched hosts has been limited however, due to the absence of an appropriate method for abrogating host immune rejection of implanted tissue. Immune-privileged tissue may be able to perform this protective function. Immune-privileged cells have been shown to survive allogeneic transplantation and to protect co-implanted tissues, such as beta islet cells. Previous work, demonstrating the use of Sertoli cells may have limited applicability due to difficulties in obtaining large amounts of immune- privileged tissue from that source and due to lack of induction of immune tolerance. We propose to determine the effectiveness of another, more readily available and immunologically useful tissue in abrogation of immune rejection of allogeneically implanted tissue. Phase II would develop co-implantation of immune-privileged cells and beta islets as a treatment modality for diabetes mellitus. PROPOSED COMMERCIAL APPLICATION: The total annual cost of treating the 14 million Americans with diabetes mellitus is approximately $120 billion. Wide swings in blood glucose levels associated with insulin injections or pump-delivery are the basis of severe secondary complications. Implanted beta islet cells protected from immune rejection by immune-privileged cells could produce the instantaneous response of the normal pancreas to changing glucose levels. The market for such implants could be $1 billion a year in the U.S. alone.

目前，用胰岛素注射或泵输送对糖尿病的治疗会导致血糖水平的巨大波动，导致与疾病相关的并发症。需要进行一种治疗，该治疗重现了正常胰腺对葡萄糖水平变化的瞬时反应。可以使用人类的Caveric Pancreata；人们实际上正在死去，他们的胰岛可能会挽救糖尿病患者的生命。但是，由于没有适当的方法来废除植入组织的免疫排斥，将β小岛移植到非MHC匹配的宿主中受到限制。免疫特你的组织可能能够执行此保护功能。已显示免疫特异性细胞可在同种异体移植中存活并保护共同植入的组织，例如β胰岛细胞。先前的工作，证明使用Sertoli细胞的使用可能有限，因为难以从该来源获得大量免疫特权组织，并且由于缺乏免疫耐受性的诱导。 我们建议确定另一个更容易获得和免疫学的组织在废除同种植入组织的免疫排斥中的有效性。第二阶段将发展免疫特异性细胞和β胰岛作为糖尿病的治疗方式的共同植入。拟议的商业应用程序：治疗1400万美国人患有糖尿病的总成本约为1,200亿美元。与胰岛素注射或泵送相关的血糖水平的宽大波动是严重的继发并发症的基础。植入的β小胰岛细胞免受免疫偏离细胞的免疫排斥性，可能会产生正常胰腺对葡萄糖水平变化的瞬时反应。仅在美国，这种植入物的市场每年可能是10亿美元。