Novel non-heart-beating donor kidney storage medium

新型无心跳供肾存储介质

• 批准号: 6443551
• 负责人: SUMI C CHEN
• 金额: $ 16.96万
• 依托单位: CHEN LABORATORIES, INC.
• 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 2002-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443551
• 关键词: animal tissue; beta hydroxybutyrate; biotechnology; kidney; kidney function; nicotinamide; technology /technique development; tissue /organ preservation

Donor kidney cannot meet current demand for kidney transplantation, the most effective for end stage renal failure. Non-heart-beating (NHB) donor kidneys are under-utilized because current technology does not allow NHB donor organs to withstand unavoidable extended periods of warm and cold ischemia. Chen Medium (CM), a novel physiological preservation solution, is highly effective for human donor cornea storage and preservation. CM contains beta-hydroxybutyrate, a unique non- lactate-generating high-energy metabolite that enables tissues to generate high levels of ATP while suppressing intracellular acidosis. NHB donor organs undergo unique metabolic compromise, many aspects of which could be prevented by nicotinamide. Nicotinamide, an NAD+ precursor that is safe for humans, is idea for MHB donor organ preservation because it scavenges free radicals, preserves NDA+ levels through inhibition of poly(ADP-ribose) polymerase-mediated NAD+ catabolism, and inhibits both inducible nitric oxide synthase and expression of leukocyte-attracting molecules on human endothelial cells after injury. We propose to use physiological, biochemical and histological criteria with the isolated perfused pig kidney model to demonstrate that CM with nicotinamide is superior to UW and EC solutions for NHB donor organ preservation. Our aim is to advance transplant technology to allow effective utilization of under-utilized NHD donor organs. PROPOSED COMMERCIAL APPLICATIONS: The proposed research, if successful, will have potential commercial application. That is, CM will be able to be marked as a non-heart-beating kidney preservation medium. This is an Orphan product with a market size estimated about $20 million a year in the US and about $6-10 million for the foreign markers combined.

供肾不能满足当前对终末期肾衰竭最有效的肾移植的需求。无心跳 (NHB) 供体肾脏未得到充分利用，因为当前技术不允许 NHB 供体器官承受不可避免的长时间热缺血和冷缺血。 Chen Medium（CM）是一种新型生理保存液，对于人供体角膜的保存和保存非常有效。 CM 含有 β-羟基丁酸，这是一种独特的不产生乳酸的高能代谢物，使组织能够产生高水平的 ATP，同时抑制细胞内酸中毒。 NHB 供体器官经历独特的代谢损害，烟酰胺可以预防其中的许多方面。烟酰胺是一种对人类安全的 NAD+ 前体，是 MHB 供体器官保存的理想选择，因为它可以清除自由基，通过抑制聚（ADP-核糖）聚合酶介导的 NAD+ 分解代谢来保留 NDA+ 水平，并抑制诱导型一氧化氮合酶和人内皮细胞上白细胞吸引分子的表达。 受伤。我们建议使用生理、生化和组织学标准与离体灌注猪肾模型来证明含有烟酰胺的 CM 在 NHB 供体器官保存方面优于 UW 和 EC 溶液。我们的目标是推进移植技术，以有效利用未充分利用的 NHD 供体器官。拟议的商业应用：拟议的研究如果成功，将具有潜在的商业应用。也就是说，CM将能够被标记为无心跳肾脏保存介质。这是一种孤儿产品，在美国的市场规模估计约为每年 2000 万美元，国外市场的市场规模合计约为 6-1000 万美元。