New Approaches to Tissue Repair

描述（由申请人提供）：罗杰威廉姆斯医疗中心的COBRE可以声称取得了很高的成功，这可以通过几个关键的基准来证明：a）年轻研究者的成功发展。所有最初的三个项目负责人和随后招募的两个项目负责人都接受了作为Pi的外部资金（总共两个ROT，三个科斯，一个R21和一个KOS）。 U19）。一个试点项目的主要研究员获得了为期3年的基金会资助; B）一批关键的高级和初级研究人员;以及c）对我们非常致力于研究的机构的科学基础设施产生了重大影响。从一开始，COBRE的基本主题就一直是组织修复和再生，最初的平行重点是干细胞生物学的新方面。随着眼镜蛇的进化， 修复主题已经变得更加强大，并且该应用高度集中于组织修复的新方法。主要研究者Vincent Falanga博士因其在组织修复和受损愈合方面的工作而享誉国际，并在指导初级研究者方面有着长期而成功的记录。继续使用涉及外科，医学，病理学，皮肤学和血液学的多学科方法，这种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，并成为组织修复领域的主要区域，国家和国际力量。COBRE更新有三个具体目标：1）继续发展和维持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; 3）维持组织修复卓越中心的多机构维度。有五个项目涉及a）造血干细胞和后代如何在组织损伤后产生功能性成纤维细胞的新测定; B）开发双特异性抗体以吸引干细胞、巨噬细胞到损伤的肌肉和皮肤的提议，以及这如何能够导致更好地理解组织修复中的细胞募集; c）在慢性不愈合伤口中使用培养的自体间充质干细胞，结合使用可预测愈合的分子标记物的人类临床试验; d）通过使用腺病毒驱动的细胞因子和内皮细胞/祖细胞募集在缺血模型中预制啮齿动物皮瓣;和e）通过与骨髓及其亚群共培养来恢复胰岛细胞的功能。这些科学项目由3个核心支持：行政核心;流式细胞术和细胞分选核心;成像和免疫组织化学核心。 正如提议的那样，COBRE的更新将继续加强机构研究活动，并有独特的机会为组织修复的多个方面做出重大贡献，并成为重要的国家和区域资源。

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.