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.