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

描述(由申请人提供)：这是一个R21应用程序，用于测试以下假设：利用现成的成体干细胞/祖细胞或细胞响应受损组织信号产生的治疗性蛋白质，可以开发出有效的新疗法来治疗非感染性角膜炎症性疾病。这一假设将通过(A)美国国家科学院院士PI和一位训练有素的眼科医生和科学家(Joo Youn oh，共同调查员)之间的合作进行验证，PI是成人干细胞/祖细胞研究的先驱，被称为MSCs。这一假说是基于oh博士的一项戏剧性发现，即在大鼠的角膜受到化学烧伤后，应用MSCs或来自MSCs的条件培养液可以减少炎症和新生血管(oh等人，2008；oh等人，2009)。目的1.验证一种假设，即在培养中预激活以表达治疗性蛋白的MSCs在减少化学性角膜损伤后的炎症和新生血管方面将比以前使用的标准MSCs培养更有效(oh等，2008)。目的2.通过应用由活化的MSCs产生的两种治疗性蛋白：抗炎蛋白TSG-6和/或抗凋亡蛋白STC-1来验证可以减少角膜炎症和新生血管的假设。目的3.使用PI以前成功采用的策略来寻找MSCs在角膜损伤反应中产生的其他治疗因子。重要意义：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900万患有干眼综合症的美国人提供更有效的治疗基础。 与公共健康相关：从生活质量恶化的疾病(如干眼)到威胁视力的疾病(如化学烧伤)，目前尚无有效和安全的角膜表面疾病治疗策略。这些情况大多伴有非感染性角膜炎症和伤口愈合缺陷。这是一个R21应用程序，用来测试一种假设，即可以利用现成的成体干细胞/祖细胞或细胞产生的治疗蛋白质来对受损组织的信号做出反应，从而开发出有效的新疗法来治疗角膜的非感染性炎症性疾病。如果成功，这项申请将为更有效地治疗每年遭受急性和严重角膜损伤的75万美国人以及900万患有干眼综合症的美国人提供基础。

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.