This application to establish an IR-BU Planning Center is based on the explicit assumption that more widespread clinical applications of regenerative medicine technologies are contingent on an improved understanding of the organ regeneration and repair process in relevant model svstems. To this end, we have assembled an interdisciplinary team that is uniquely qualified to pursue the focused aims of this Planning Center. The key personnel on the Planning Center team reflect an ideal union of investigators with extensive and complementary experience in research and clinical translation in the lower urinary tract, with recognized expertise in stem cell tjiology), contribution and composition of tumor formation, as well as the role of stem cells and gene therapy in liver regeneration and hematopoiesis. An Educational Enrichment Program is proposed to increase institutional, national and international recognition of our efforts, and moreover, to provide an excellent environment and resources for training the next generation of translational urologic researchers. The scientific project specifically targets the estimated 35 million Americans that suffer from bladder disease, most of which are chronic conditions (i.e., infections, congenital disorders, and inflammation) that ultimately compromise cellular and tissue integrity leading to reduced bladder function, as well as a diminished quality of life for millions of patients. Despite our encouraging advancements in functional bladder regeneration in rats, it remains obvious that development of additional animal models is necessary to accelerate the pace of scientific progress toward clinical translation. To this end we propose the use of multicolored transplant procedures that will, for the first time, allow the identification of what cells or tissue is responsible for the bladder repair/regeneration processes. Thus, we will incorporate novel imaging technology into our ongoing studies of functional bladder regeneration to provide an interdisciplinary approach to the study of bladder wall regeneration and repair as follows:
Specific Aim #1 : Evaluate and quantify the spatial and temporal characteristics of the cellular proliferation that mediates functional bladder regeneration in the mouse model.
Specific Aim #2 : Determine the contribution of local stem/progenitor cells versus bone marrow-derived stem/progenitor cells to proliferative remodeling of the bladder wall in mice in response to a continuum of njuries/defects.
Congenital deformities, infection, inflammation, traumatic injury, cancer and nerve lesions produce irreversible damage to bladder tissue resulting in removal and/or permanent impairment in bladder function. These conditions affect millions of Americans and lead to a poor quality of life. We will study the process of bladder regeneration in a relevant rodent model to better apply tissue engineering and regenerative medicine technologies to the creation of new functional tissue derived from the patients'own cells.
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