Adult Progenitors in Kidney Tubulointerstitium

肾小管间质中的成体祖细胞

基本信息

批准号：
9546278
负责人：
BENJAMIN D. HUMPHREYS
金额：
$ 31.3万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-23 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9546278
关键词：
3-Dimensional Ablation Acute Address Adult Architecture Basement membrane Behavior Biological Assay Blood Vessels Blood capillaries CSPG4 gene Caliber Cell Separation Cell physiology Cells Chronic Coculture Techniques Data Deposition Desmin Disease Disease Progression Endothelial Cells Engineering Epithelial Epithelial Cells Fibrosis Future Genetic Health Hypoxia In Vitro Injury Integrins Kidney Kidney Failure Knock-in Label Measures Medical Mesenchymal Mesenchymal Stem Cells Modeling Morphology Mouse Strains Mus Muscle Cells Myofibroblast Natural regeneration Nephrons Pericytes Phase Play Population Property Protocols documentation Quality Control Regenerative Medicine Role Stem cells Study models System Techniques Testing Therapeutic Tissues Transplantation Tube Tubular formation United States Up-Regulation Vascular Endothelial Cell Vascular Smooth Muscle calponin capillary cell type design experimental study healing in vivo injured interstitial kidney cell kidney repair member novel novel strategies progenitor public health relevance rat KIM-1 protein regenerative regenerative therapy repaired scaffold stromal progenitor therapeutic target tool transcriptome

项目摘要

DESCRIPTION (provided by applicant): Kidney failure is a critical health problem in the United States and it reflects the consequences of failed nephron repair and progressive fibrosis. Two promising strategies to treat kidney failure include regeneration of functional nephrons in vivo, and engineering of transplantable nephrons in vitro. We have identified two critical adult kidney progenitor populations with strong potential to play important roles in each strategy. Within the tubule, we have previously shown that dedifferentiated proximal tubule cells are responsible for repairing proximal tubule by proliferative expansion. We have now generated a novel approach to easily isolate a pure population of these dedifferentiated epithelial progenitors, and we will characterize, culture and define the functional properties of these critical cells. In addition, we have recently identified a kidney resident mesenchymal stem cell population defined by expression of Gli1 that represents the major myofibroblast precursor population in fibrotic disease. These cells have vascular stabilizing properties and are capable of differentiating into both pericytes and vascular smooth muscle cells. We will further characterize the function of these cells both in vitro and in vivo, and coculture them with endothelial cells and epithelial cels to model the kidney tubulointerstitium in vitro. Together, the proposed experiments will not only define novel regenerative strategies for kidney failure, but will also validate two critical adult progenitor cell populations that will be useful for a variety of regenerative approaches to treat kidney failure.

描述（由适用提供）：肾衰竭是美国的一个关键健康问题，它反映了肾脏修复和进行性纤维化失败的后果。治疗肾脏衰竭的两种有希望的策略包括体内功能性肾脏的再生，以及在体外的可移植肾脏的工程。我们已经确定了两个关键的成人肾脏祖先种群，在每种策略中都起着重要作用。在管中，我们先前已经表明，去分化的近端管细胞负责通过增殖膨胀来修复近端管。现在，我们已经生成了一种新型方法，可以轻松分离这些去分化上皮祖细胞的纯种群，我们将表征，培养并定义这些关键细胞的功能特性。另外，我们最近，已经确定了由GLI1表达定义的肾脏居民间充质干细胞群，该表达代表了纤维化疾病中主要的肌纤维细胞前体群体。这些细胞具有血管稳定的特性，并且能够区分周细胞和血管平滑肌细胞。我们将进一步表征这些细胞在体外和体内的功能，并与内皮细胞和上皮凝胶共培养，以在体外对肾脏tubeloninterntrosstitium进行建模。共同提出的实验不仅将定义肾衰竭的新型再生策略，而且还将验证两个关键的成年祖细胞群体，这些祖细胞群对于治疗肾衰竭的各种再生方法将很有用。