Regeneration, Repair and Remodeling of the Lower Urinary Tract

这项建立IR-BU规划中心的申请是基于明确的假设，即更多 再生医学技术的广泛临床应用取决于技术的改进 了解相关模型系统中的器官再生和修复过程。为此，我们有 组建了一支具有独特资质的跨学科团队，以实现本规划的重点目标 中心。规划中心团队的关键人员反映了调查人员与广泛的 以及在下尿路研究和临床翻译方面的补充经验，并得到认可 干细胞学专业知识)，肿瘤形成的贡献和组成，以及干细胞的作用 肝再生和造血中的细胞和基因治疗。一项教育充实计划是 建议增加机构、国家和国际社会对我们努力的认可，此外， 为培训下一代转化型泌尿外科提供良好的环境和资源 研究人员。该科学项目专门针对大约3500万美国人，他们患有 膀胱疾病，其中大部分是慢性疾病(即感染、先天性疾病和 炎症)，最终损害细胞和组织的完整性，导致膀胱功能降低，如 以及数百万患者的生活质量下降。尽管我们在以下方面取得了令人鼓舞的进展 在大鼠的功能性膀胱再生中，仍然明显地发展了额外的动物模型 有必要加快临床翻译的科学进步步伐。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 组织负责膀胱修复/再生过程。因此，我们将结合新的成像技术 技术为我们正在进行的功能性膀胱再生研究提供了一个跨学科的 膀胱壁再生和修复的研究方法如下： 具体目标1：评估和量化细胞增殖的空间和时间特征 在小鼠模型中调节功能性膀胱再生。 具体目标#2：确定局部干/祖细胞与骨髓来源的干细胞的贡献 干细胞/祖细胞对小鼠膀胱壁增殖性重塑的影响 损害/缺陷。

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.