Regeneration, Repair and Remodeling of the Lower Urinary Tract

下尿路的再生、修复和重塑

• 批准号: 8447148
• 负责人: George Joseph Christ
• 金额: $ 29.6万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-29 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8447148
• 关键词: Accounting; Affect; American; Animal Model; Animals; Asses; Biological Models; Bladder; Bladder Diseases; Bladder Injury; Bladder Tissue; Bone Marrow; Bromodeoxyuridine; Cell Proliferation; Cells; Characteristics; Chronic; Clinical; Congenital Abnormality; Congenital Disorders; Data; Defect; Development; Environment; Etiology; Excision; Female; Future; Glean; Goals; Growth; Hematopoiesis; Housing; Human Resources; Imaging technology; Impairment; Infection; Inflammation; Injury; International; Investigation; Label; Lamina Propria; Lead; Lesion; Light; Liver Regeneration; Location; Lower urinary tract; Malignant Neoplasms; Mediating; Methodology; Modeling; Molecular Genetics; Monitor; Mus; Natural regeneration; Nature; Nerve; Operative Surgical Procedures; Patients; Population; Procedures; Process; Qualifying; Quality of life; Rattus; Regenerative Medicine; Relative (related person); Research; Research Personnel; Resources; Rodent Model; Role; Staging; Stem cells; Technology; Testing; Thick; Time; Tissue Engineering; Tissue Transplantation; Tissues; Training; Translations; Transplantation; Urothelium; Work; base; bone; clinical application; experience; gene therapy; implantation; improved; in vivo; insight; interdisciplinary approach; male; mouse model; next generation; novel; novel therapeutics; optical imaging; organ regeneration; progenitor; programs; public health relevance; reconstitution; repaired; response; stem; tumor; urologic

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.

描述（由申请人提供）：建立 IR-BU 规划中心的申请基于这样一个明确的假设：再生医学技术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团队，他们具有独特的资格来实现该规划中心的重点目标。规划中心团队的关键人员体现了一个理想的研究人员联盟，他们在下尿路研究和临床转化方面拥有丰富且互补的经验，在干细胞病因学、肿瘤形成的贡献和组成、以及干细胞和基因治疗在肝再生和造血中的作用方面具有公认的专业知识。提出了一项教育丰富计划，以提高机构、国家和国际对我们努力的认可，此外，为培训下一代转化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估计有 3500 万患有膀胱疾病的美国人，其中大多数是慢性疾病（即感染、先天性疾病和炎症），这些疾病最终会损害细胞和组织的完整性，导致膀胱功能下降，并导致数百万患者的生活质量下降。尽管我们鼓励 尽管大鼠功能性膀胱再生取得了进展，但显然有必要开发更多的动物模型，以加快临床转化的科学进展步伐。为此，我们建议使用彩色移植程序，这将首次允许识别哪些细胞或组织负责修复/再生过程。因此，我们将把新颖的成像技术纳入我们正在进行的功能性膀胱再生研究中，为膀胱壁再生和修复的研究提供跨学科方法，如下： 具体目标#1：评估和量化介导小鼠模型功能性膀胱再生的细胞增殖的空间和时间特征。 具体目标#2：确定局部干/祖细胞与骨髓来源的干/祖细胞的贡献。