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

描述（由申请人提供）：这是一份R21申请，旨在测试一种假设，即利用现成的成体干细胞/祖细胞或细胞根据受伤组织的信号产生的治疗蛋白，可以开发出有效的新疗法来治疗角膜非感染性炎症性疾病。该假设将通过以下两方面的合作进行验证：(a) PI是美国国家科学院的成员，他一直是研究成体干细胞/祖细胞（MSCs）的先驱；(b)一位训练有素的眼科医生和科学家（Joo Youn Oh，共同研究员）。该假设基于Dr.Oh的惊人发现，即在大鼠角膜化学烧伤后，应用间充质干细胞或间充质干细胞的条件培养基可减少炎症和新生血管（Oh et al., 2008; Oh et al., 2009）。目的1。与之前使用的MSCs标准培养物相比，在培养物中预先激活MSCs以表达治疗性蛋白，在减少化学诱导角膜损伤后的炎症和新生血管方面更有效，这一假设得到验证（Oh et al., 2008）。目标2。通过使用活化的间质干细胞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，可以减少角膜炎症和新生血管形成的假设。目标3。使用PI先前采用的成功策略来寻找MSCs在角膜损伤反应中产生的其他治疗因子。意义：如果成功，该应用将为每年75万美国人遭受急性和严重角膜损伤以及900万美国人遭受干眼综合征提供更有效的治疗基础。

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.