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送治疗糖尿病会引起血糖水平的剧烈波动，从而导致与该疾病相关的并发症。目前迫切需要一种治疗方法，能够重现正常胰腺对血糖水平变化的瞬时反应。人腹腔胰腺是可用的；人们真的会和他们的胰岛一起死去，而胰岛对糖尿病患者来说可能是挽救生命的工具。然而，由于缺乏一种适当的方法来消除宿主对移植组织的免疫排斥，将β胰岛移植到非MHC匹配的宿主中一直受到限制。具有免疫特权的组织可能能够执行这种保护功能。免疫特权细胞已被证明能在同种异体移植中存活，并保护共植入组织，如β胰岛细胞。先前的研究表明，Sertoli细胞的应用可能有限，因为很难从该来源获得大量具有免疫特权的组织，而且缺乏免疫耐受的诱导。我们建议确定另一种更容易获得和免疫有用的组织在消除同种异体移植组织的免疫排斥反应中的有效性。第二阶段将研究免疫特权细胞和胰岛的联合植入，作为糖尿病的一种治疗方式。拟议的商业应用：每年治疗1400万美国糖尿病患者的总费用约为1200亿美元。与胰岛素注射或泵送相关的血糖水平大幅波动是严重继发性并发症的基础。植入的胰岛细胞受到免疫特权细胞的保护，免受免疫排斥，可以产生正常胰腺对血糖水平变化的即时反应。仅在美国，这种植入物每年的市场规模就可能达到10亿美元。