New Approaches to Tissue Repair

罗杰·威廉姆斯医疗中心的COBRE可以宣称取得了很高的成功，几个关键基准证明了这一点：a)成功培养了年轻的研究人员。所有最初的三位项目负责人和后来招募的两位项目负责人都以Pi的身份获得了外部资助（总共有两位rot，三位KOS，一位R21和一位U19）。一名飞行员的PI获得3年的基金会奖助金；b)高级和初级调查人员的临界数量；c)对我们非常投入的机构的科学基础设施产生重大影响。从一开始，COBRE的基本主题是组织修复和再生，最初平行强调干细胞生物学的新方面。随着COBRE的发展，组织修复主题变得更加强烈，这一应用高度关注于组织修复的新方法。私家侦探文森特·法兰加博士因其在组织修复和损伤愈合方面的工作而享誉国际，并在指导初级调查人员方面有着长期而成功的记录。继续使用包括外科、医学、病理学、皮肤病学和血液学在内的多学科方法，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，并成为组织修复领域的主要地区、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卓越的组织修复研究中心；2)成为组织修复领域初级研究人员培训的领先中心；3)维持我们卓越的组织修复中心的多机构维度。有五个项目涉及：a)对组织损伤后造血干细胞及其后代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、巨噬细胞到受损肌肉和皮肤的建议，以及这如何能够更好地理解组织修复中的细胞募集；C)使用培养的自体间充质干细胞治疗慢性不愈合伤口的人体临床试验，并结合使用可能预测愈合的分子标记；D)利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；e)与骨髓及其亚群共培养的胰岛细胞功能恢复。这些科研项目有三个核心支撑：行政核心；流式细胞仪及细胞分选芯；成像和免疫组化核心。

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.