Chimeric Kidney

嵌合肾

• 批准号: 6466321
• 负责人: Marc Randall Hammerman
• 金额: $ 15.32万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6466321
• 关键词: clearance rate; embryo /fetus tissue transplantation; growth /development; growth factor; histogenesis; homologous transplantation; immune tolerance /unresponsiveness; inulin; kidney function; kidney transplantation; laboratory mouse; laboratory rat; tissue mosaicism; xenotransplantation

DESCRIPTION (provided by applicant): In studies that provide the background for this application we have transplanted rat metanephric allografts and xenografts into adult rodent hosts. We have established that: 1) metanephroi can be transplanted into the omentum of outbred or inbred rats without the use of immune suppression such that they undergo growth and differentiation in hosts, acquire a blood supply from the host, and clear inulin from the host's circulation; 2) metanephroi can be transplanted across the rat MHC and this is possible because of a state of peripheral tolerance due to T cell ignorance; 3) metanephroi can be stored in vitro for at least 3 days prior to transplantation without affecting growth, development and function in hosts; 4) xenotransplantation of metanephroi across a concordant barrier (rat to mouse) can be performed; and 5) inulin clearances of transplanted metanephroi (rat to rat) can be increased, using growth factors, by a factor of 225 relative to clearances obtained in the original group of transplants. The overall unifying hypothesis to be tested by studies outlined in this competitive renewal application is that renal fnction sufficient to sustain life can result from allograft metanephroi transplanted into the abdominal cavity of adult rats after native kidneys are removed. To this end, the Principal Investigator proposes to carry out a series of investigations the specific aim of which is to determine whether growth factors and renal growth promoting agents can enhance the development growth and function of transplanted allograft metanephroi such that such one or two transplanted developed metanephroi can sustain life in a rat after native kidneys are removed. Our studies will provide insight into the physiology and feasibility of a novel means of renal transplantation that could be applied to humans.

描述（由申请人提供）：在提供背景的研究中 该应用我们已经移植了大鼠元素同种异体移植物和异种移植物 进入成年啮齿动物宿主。我们已经确定：1）Metanephroi可以 不用 免疫抑制使其在宿主中经历生长和分化， 从宿主那里获取血液供应，并从主机上清除丁素 循环; 2）可以在大鼠MHC上移植Metanephroi，这是 由于T细胞无知引起的外围耐受性状态可能是可能的； 3） Metanephroi可以在移植前至少存储至少3天 不影响宿主的生长，发展和功能； 4） 一致性屏障的替诺普罗伊的异种移植（老鼠） 可以执行； 5）移植的替诺普罗（大鼠到 使用生长因子可以增加大鼠）相对于225倍 在原始的移植组中获得的间隙。整体统一 通过此竞争更新中概述的研究将测试的假设 应用是，肾脏足以维持生命。 同种异体移植物属于移植到成年大鼠的腹腔 去除本地肾脏后。为此，主要调查员 建议进行一系列调查的具体目的是 确定生长因素和肾脏生长促进剂是否可以 增强移植同种异体移植的发育生长和功能 metanephroi使得这样的一两个移植的发达的元素可以 去除本地肾脏后，在老鼠中维持生命。我们的研究将 提供有关新型肾脏手段的生理学和可行性的见解 可以应用于人类的移植。