Regeneration, Repair and Remodeling of the Lower Urinary Tract

描述(申请人提供)：申请建立IR-BU规划中心是基于这样一个明确的假设，即再生医学技术的更广泛的临床应用取决于对相关模型系统中器官再生和修复过程的更好理解。为此，我们组建了一支跨学科的团队，这支团队唯一有资格实现这个规划中心的重点目标。规划中心团队的关键人员反映了研究人员的理想组合，他们在下尿路研究和临床翻译方面拥有广泛和互补的经验，在干细胞病因学方面具有公认的专业知识，在肿瘤形成的贡献和构成方面，以及干细胞和基因疗法在肝脏再生和造血中的作用。提出了一个教育充实计划，以增加机构、国家和国际对我们努力的认可，并为培训下一代转化型泌尿外科研究人员提供良好的环境和资源。该科学项目专门针对大约3500万患有膀胱病的美国人，其中大多数是慢性疾病(即感染、先天性疾病和炎症)，最终会损害细胞和组织的完整性，导致膀胱功能下降，以及数百万患者的生活质量下降。尽管我们鼓舞人心 尽管在大鼠功能性膀胱再生方面取得了进展，但很明显，开发更多的动物模型对于加快临床转化的科学进步步伐仍然是必要的。为此，我们建议使用五颜六色的移植程序，这将首次允许识别哪些细胞或组织负责更糟糕的修复/再生过程。因此，我们将把新的成像技术融入我们正在进行的功能性膀胱再生研究中，以提供一种跨学科的方法来研究膀胱壁的再生和修复，如下所示： 具体目标#1：在小鼠模型中评估和量化细胞增殖的空间和时间特征，该细胞增殖介导功能性膀胱再生。 具体目标#2：确定局部干细胞/祖细胞相对于骨髓来源的干细胞/祖细胞的贡献。

DESCRIPTION (provided by applicant): 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 systems. 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 etiology), 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 badder 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.