PLACENTAL CELLS FOR PROTECTION OF IMPLANTED B ISLETS

目前用胰岛素注射或泵输送治疗糖尿病引起血糖水平的大幅波动，这导致与疾病相关的并发症。非常需要一种治疗方法，能够再现正常胰腺对葡萄糖水平变化的瞬时反应。人类的海绵体胰腺是可用的;人们实际上是沿着他们的胰岛而死，而这些胰岛可能对糖尿病患者有救命的作用。然而，由于缺乏消除植入组织的宿主免疫排斥的适当方法，将β胰岛移植到非MHC匹配的宿主中受到限制。免疫特权组织可能能够执行这种保护功能。免疫豁免细胞已被证明在同种异体移植中存活并保护共同植入的组织，如β胰岛细胞。先前的工作证明了支持细胞的使用可能具有有限的适用性，这是由于难以从该来源获得大量免疫豁免组织以及由于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学上有用的组织在消除同种异体植入组织的免疫排斥反应中的有效性。第二阶段将开发免疫特权细胞和β胰岛的共同植入作为糖尿病的治疗方式。建议的商业应用：每年治疗1400万美国糖尿病患者的总费用约为1200亿美元。与胰岛素注射或泵输送相关的血糖水平的大幅波动是严重继发性并发症的基础。植入的胰岛β细胞受到免疫豁免细胞的免疫排斥，可以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就可能达到10亿美元。

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.