Adult Stem Cells/Progenitor Cells for Treatment of Corneal Injuries and Diseases

描述（由申请人提供）：这是一项R21申请，旨在检验以下假设：可以利用现成的成体干/祖细胞或细胞响应来自受损组织的信号产生的治疗性蛋白质开发出有效的新疗法，用于治疗角膜的非感染性炎症性疾病。该假设将通过以下人员之间的合作进行检验：（a）PI，美国国家科学院院士，是成人干/祖细胞（称为MSC）研究的先驱;（B）一名训练有素的眼科医生和科学家（Joo Youn Oh，共同研究者）。该假设基于Dr.Oh的戏剧性发现，即在大鼠角膜化学烧伤后，应用MSC或来自MSC的条件培养基减少了炎症和新血管形成（Oh等人，2008; Oh等人，2009年）的报告。目标1.测试以下假设：在培养物中预活化以表达治疗性蛋白质的MSC在减少化学诱导的角膜损伤后的炎症和新血管形成方面将比先前使用的MSC的标准培养物更有效（Oh等人，2008年）。目标二。测试角膜的炎症和新血管形成可以通过应用由活化的MSC产生的两种治疗性蛋白质来减少的假设：抗炎蛋白质TSG-6和/或抗凋亡蛋白质STC-1。目标3：使用PI采用的先前成功的策略来搜索MSC响应角膜损伤产生的其他治疗因子。重要性：如果成功，该应用将为每年遭受急性和严重角膜损伤的75万美国人以及患有干眼综合征的900万美国人提供更有效的治疗方法。 公共卫生相关性：对于角膜表面疾病，从生活质量恶化的病症（例如干眼症）到威胁视力的病症（例如化学烧伤），没有有效和安全的治疗策略。这些病症中的大多数伴有非感染性角膜炎症和伤口愈合缺陷。这是一个R21的应用程序，以测试的假设，有效的新疗法可以开发用于非感染性炎症性疾病的角膜，无论是现成的成人干细胞/祖细胞或治疗性蛋白质的细胞产生的反应，从受伤的组织的信号。如果成功，该应用将为每年遭受急性和严重角膜损伤的75万美国人以及患有干眼综合征的900万美国人提供更有效的治疗方法。

DESCRIPTION (provided by applicant): This is a R21 application to test the hypothesis that effective new therapies can be developed for noninfectious inflammatory diseases of the cornea with either readily available adult stem/progenitor cells or the therapeutic proteins the cells produce in response to signals from injured tissues. The hypothesis will be tested through a collaboration between (a) the PI, a member of the National Academy of Sciences, who has been a pioneer in research with adult stem/progenitor cells known as MSCs, and (b) a fully-trained ophthalmologist and scientist (Joo Youn Oh, Co-Investigator). The hypothesis is based on the dramatic discovery by Dr.Oh that after a chemical burn to the cornea of a rat, application of MSCs or conditioned medium from MSCs reduced inflammation and neovascularization (Oh et al., 2008; Oh et al., 2009). Aim 1. Test the hypothesis that MSCs pre-activated in culture to express therapeutic proteins will be more effective in reducing inflammation and neovascularization following chemically-induced injury to the cornea than the standard cultures of MSCs used previously (Oh et al., 2008). Aim 2. Test the hypothesis that inflammation and neovascularization of the cornea can be reduced by application of two of the therapeutic proteins produced by activated MSCs: the anti- inflammatory protein TSG-6 and/or the anti-apoptotic protein STC-1. Aim 3. Use a previously successful strategy employed by the PI to search for additional therapeutic factors produced by MSCs in response to corneal injury. SIGNIFICANCE: If successful, the application will provide a basis for more effective therapies for the 750,000 Americans who each year suffer from acute and severe injuries of the cornea and for the 9 million Americans who suffer from dry eye syndrome. PUBLIC HEALTH RELEVANCE: There are no efficient and safe therapeutic strategies for corneal surface diseases ranging from quality-of-life deteriorating conditions (e.g. dry eye) to vision-threatening conditions (e.g. chemical burn). Most of these conditions are accompanied by noninfectious corneal inflammation and wound healing defects. This is a R21 application to test the hypothesis that effective new therapies can be developed for noninfectious inflammatory diseases of the cornea with either readily available adult stem/progenitor cells or the therapeutic proteins the cells produce in response to signals from injured tissues. If successful, the application will provide a basis for more effective therapies for the 750,000 Americans who each year suffer from acute and severe injuries of the cornea and for the 9 million Americans who suffer from dry eye syndrome.