New Approaches to Tissue Repair

描述(由申请人提供)：罗杰·威廉姆斯医学中心的科布雷可以声称取得了很高的成功，几个关键基准证明了这一点：a)年轻研究人员的成功发展。最初的三名项目负责人和后来招募的两名项目负责人都获得了作为PI的外部资金(总共两个ROT、三个KO、一个R21和一个 U19)。一名飞行员的PI获得了为期3年的基金会拨款；b)大量的高级和初级调查人员；以及c)对我们非常坚定的机构的科学基础设施的重大影响。从一开始，Cobre的基本主题就是组织修复和再生，最初的重点是干细胞生物学的新方面。随着眼镜蛇的进化，这些组织 修复主题已经变得更加强大，这一应用高度关注组织修复的新方法。私家侦探文森特·法兰加博士因其在组织修复和受损愈合方面的工作而闻名国际，并在指导初级调查人员方面有着长期和成功的记录。继续使用涉及外科、医学、病理学、皮肤科和血液学的多学科方法，这一更新应用强调组织修复、其生物学和治疗机会。总体目标是继续发展初级研究人员，成为组织修复领域的一支主要的地区、国家和国际力量。Cobre的更新有三个具体目标：1)继续发展和维持一个组织修复卓越研究中心；2)成为组织修复领域初级研究人员培训的领先中心；以及3)保持我们组织修复卓越中心的多机构维度。有五个项目涉及a)关于造血干细胞和后代在组织损伤后如何产生功能性成纤维细胞的新确定；b)开发双特异性抗体以吸引干细胞和巨噬细胞到受伤的肌肉和皮肤，以及这如何有助于更好地了解组织修复中的细胞招募；c)在慢性不可愈合伤口中使用培养的自体间充质干细胞的人体临床试验，结合使用可以预测愈合的分子标志物；d)使用腺病毒驱动的细胞因子和内皮细胞/祖细胞招募在缺血模型中预制啮齿类动物皮瓣；和e)通过与骨髓及其亚群共培养恢复胰岛细胞的功能。这些科学项目由三个核心支持：行政核心；流式细胞仪和细胞分选核心；成像和免疫组织化学核心。 按照提议，科布雷更新将继续加强机构研究活动，并拥有独特的机会，为组织修复的多个方面做出重大贡献，并成为州和地区的重要资源。

DESCRIPTION (provided by applicant): The COBRE at Roger Williams Medical Center can claim a high level of success, as evidenced by several critical benchmarks: a) Successful development of young investigators. All the initial three projects leaders and the two subsequently recruited project leaders have received external funding as Pi's (total of two ROTs, three KOS's, one R21, and one U19). The PI of a pilot received a 3-year Foundation grant; b) A critical mass of senior and junior investigators; and c) A major impact on the scientific infrastructure of our very committed institution. From the inception, the underlying theme of the COBRE has been tissue repair and regeneration, with an initial parallel emphasis on new aspects of stem cell biology. As the COBRE evolved, the tissue repair theme has emerged stronger, and this application is highly focused on new approaches to tissue repair. The PI, Dr. Vincent Falanga, is internationally known for his work in tissue repair and impaired healing and has a long and successful track record for mentorship of junior investigators. Continuing to use a multidisciplinary approach involving surgery, medicine, pathology, dermatology, and hematology, this renewal application emphasizes tissue repair, its biology, and therapeutic opportunities. The overall goal is to continue the development of junior investigators and to become a major regional, national, and international force in tissue repair. The COBRE renewal has three specific aims: 1) To continue to develop and sustain a center of research excellence in tissue repair 2) To be a leading center in the training of junior investigators in the field of tissue repair; and 3) To sustain a multi-institutional dimension to our center of excellence in tissue repair. There are five projects involving a) a novel determination of how hematopoietic stem cells and progeny can give rise to functional fibroblasts after tissue injury; b) a proposal to develop bispecific antibodies to attract stem cells, macrophages to injured muscle and skin, and how this could lead to better understanding of cell recruitment in tissue repair; c) a human clinical trial of the use of cultured autologous mesenchymal stem cells in chronic non-healing wounds, combined with the use of molecular markers that may predict healing; d) prefabrication of rodent flaps in an ischemic model by the use of adenovirally-driven cytokines and endothelial cell/progenitor recruitment; and e) functional restoration of pancreatic islet cells by co-culture with bone marrow and its subpopulations. These scientific projects are supported by 3 cores: administrative core; flow cytometry and cell sorting core; imaging and immunohistochemistry core. As proposed, the COBRE renewal will continue to strengthen the institutional research activities and has a unique opportunity to make a major contribution to multiple aspects of tissue repair and be an important state and regional resource.