Use of recombinant human lactoferrin for wounds by stimulating cell growth

重组人乳铁蛋白通过刺激细胞生长用于治疗伤口

• 批准号: 7159482
• 负责人: NING HUANG
• 金额: $ 11.39万
• 依托单位: VENTRIA BIOSCIENCE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2008-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7159482
• 关键词: bioengineering /biomedical engineering; cell migration; cell proliferation; drug design /synthesis /production; fibroblasts; genetically modified plants; human genetic material tag; keratinocyte; lactoferrin; method development; protein purification; recombinant proteins; rice; skin; therapy design /development; tissue /cell culture; wound healing

DESCRIPTION (provided by applicant): Project Summary/Abstract: Acute and chronic wound care continues to pose major challenges in both civilian and military forces. It is estimated that 6 million people in the United States were affected by chronic wounds, such as venous ulcers. As of November 2005, 15,568 US soldiers in Operation Iraqi Freedom were wounded and about 50% of the injured were unable to return to duty within 72 hours of injury. Wounds, acute or chronic, not only threaten the life of the wounded, but also increase frailty in the elderly, decrease quality of life, and loss in productivity. The high costs associated with the management of slow-healing wounds have an enormous impact on the economy. In the US alone, $2.8 billion is spent annually to treat chronic wounds and the worldwide market reaches $7 billion. This problem can partially be alleviated by rapid wound healing. Currently, extensive efforts are being made to develop growth factors as wound healing agents; however, not all studies show the same results further growth factors do not provide any antimicrobial effects to prevent infection. Delayed cell growth and migration of keratinocytes and fibroblasts and microbial infections at the wound site impairs wound healing. We propose to use lactoferrin (LF) as a novel wound healing agent based on its ability to promote cell growth and its antimicrobial properties. To test the effectiveness of LF on wound healing, recombinant human LF (rhLF), produced in rice, will be purified and examined for its effects on the proliferation and migration of human epithelial keratinocyte and fibroblast in vitro. To study the effects of rhLF on cell migration, an incisional wound cell model will be used and the migration of cells will be observed. Data from these in vitro studies will provide the fundamental basis for future investigation of rhLF on wound healing in an animal model and in humans. In addition, purification procedures developed in Phase I will be implemented in scale-up processing of rhLF for Phase II. The long term goal of this project is to commercialize a new topical agent for rapid wound healing, which would in turn decrease the burden wounds have on the economy and society. Project Narrative: The high costs associated with the management of wounds have an enormous impact on the economy. Administration of a novel topical wound healing agent, lactoferrin (LF) would promote cell growth/migration with added benefit of preventing/treating bacterial infections. The use of LF would 1) alleviate the burden wounds have on the economy and society and 2) benefit the elderly, diabetics, immunocompromised patients, and military forces injured in combat.

说明(由申请人提供)：项目摘要/摘要：急性和慢性伤口护理继续对文职和军事部队构成重大挑战。据估计，美国有600万人受到静脉溃疡等慢性伤口的影响。截至2005年11月，在伊拉克自由行动中有15,568名美军士兵受伤，约50%的伤者在受伤72小时内无法返回工作岗位。无论是急性还是慢性创伤，不仅威胁着伤者的生命，而且还会增加老年人的虚弱，降低生活质量，并造成生产力的损失。与管理缓慢愈合的伤口相关的高昂成本对经济产生了巨大影响。仅在美国，每年花费28亿美元治疗慢性伤口，全球市场达到70亿美元。这个问题可以通过伤口的快速愈合得到部分缓解。目前，人们正在进行广泛的努力，以开发生长因子作为伤口愈合剂；然而，并不是所有的研究都表明同样的结果，进一步的生长因子不能提供任何预防感染的抗菌效果。伤口处角质形成细胞和成纤维细胞的细胞生长和迁移延迟以及微生物感染损害了伤口的愈合。我们建议使用乳铁蛋白(LF)作为一种新的伤口愈合剂，基于其促进细胞生长的能力和它的抗菌特性。为了验证重组人乳铁蛋白(LF)在创伤愈合中的作用，我们将从大米中提取重组人乳铁蛋白(RhLF)，并在体外检测其对人上皮角质形成细胞和成纤维细胞的增殖和迁移的影响。为了研究重组人乳铁蛋白对细胞迁移的影响，我们将采用创伤细胞模型，观察细胞的迁移情况。这些体外研究的数据将为未来在动物模型和人类中研究重组人乳铁蛋白对伤口愈合的影响提供基本的基础。此外，第一阶段开发的净化程序将在第二阶段的rhLF放大处理中实施。该项目的长期目标是将一种新的创面快速愈合的外用剂商业化，这将反过来减轻伤口对经济和社会的负担。项目简介：与伤口管理相关的高昂成本对经济产生了巨大影响。乳铁蛋白(LF)是一种新型外用创面愈合剂，可促进细胞生长/迁移，并可预防/治疗细菌感染。LF的使用将1)减轻创伤对经济和社会的负担，2)使老年人、糖尿病患者、免疫功能低下的患者和在战斗中受伤的军队受益。