Use of recombinant human lactoferrin for wounds by stimulating cell growth

项目概述/摘要：急慢性伤口护理在民用和军用部队中继续构成重大挑战。据估计，美国有600万人受到慢性伤口的影响，比如静脉溃疡。截至2005年11月，15,568名美国士兵在伊拉克自由行动中受伤，其中约50%的伤者在受伤后72小时内无法返回工作岗位。急性或慢性伤口不仅威胁到受伤者的生命，而且还会使老年人更加虚弱，降低生活质量，丧失生产力。与治疗愈合缓慢的伤口相关的高昂费用对经济产生了巨大影响。仅在美国，每年用于治疗慢性伤口的费用就高达28亿美元，全球市场达到70亿美元。伤口快速愈合可部分缓解这一问题。目前，人们正在努力开发生长因子作为伤口愈合剂；然而，并不是所有的研究都显示出相同的结果，进一步的生长因子不提供任何抗菌作用来预防感染。角质形成细胞和成纤维细胞的生长和迁移延迟以及伤口部位的微生物感染会损害伤口愈合。基于乳铁蛋白促进细胞生长和抗菌的特性，我们建议将其作为一种新型的伤口愈合剂。为了验证LF对伤口愈合的作用，我们将对从水稻中提取的重组人LF （rhLF）进行纯化，并在体外研究其对人上皮角质形成细胞和成纤维细胞增殖和迁移的影响。为了研究rhLF对细胞迁移的影响，我们将采用切口创面细胞模型，观察细胞的迁移情况。这些体外研究的数据将为rhLF对动物模型和人体伤口愈合的进一步研究提供基础基础。此外，第一期开发的净化程序将在第二期rhLF的放大处理中实施。该项目的长期目标是将一种用于伤口快速愈合的新型外用剂商业化，从而减轻伤口对经济和社会的负担。项目说明：与伤口管理相关的高成本对经济产生巨大影响。乳铁蛋白（LF）是一种新型的局部伤口愈合剂，可促进细胞生长/迁移，并具有预防/治疗细菌感染的额外益处。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、免疫功能低下患者和在战斗中受伤的军人受益。

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.