Adult Progenitors in Kidney Tubulointerstitium

肾小管间质中的成体祖细胞

基本信息

批准号：
9146936
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 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9146936
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 Failure Fibrosis Future Genetic Healed Health Hypoxia In Vitro Injury Integrins Kidney Kidney Failure Knock-in Label Measures Medical Mesenchymal Mesenchymal Stem Cells Modeling Morphology Mouse Strains Mus Myofibroblast Natural regeneration Nephrons Pericytes Phase Play Population Property Protocols documentation Quality Control Regenerative Medicine Role Smooth Muscle Myocytes 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 healing in vivo injured interstitial kidney cell kidney repair member novel novel strategies progenitor rat KIM-1 protein regenerative regenerative therapy repaired research study scaffold stem stem cell population 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（由申请人提供）：肾衰竭是美国的一个严重健康问题，它反映了肾单位修复失败和进行性纤维化的后果，治疗肾衰竭的两种有前景的策略包括功能性肾单位的体内再生和可移植性肾单位的工程设计。我们已经确定了两个关键的成年肾祖细胞群，它们在肾小管内具有很强的发挥重要作用的潜力，我们之前已经表明，去分化的近端肾小管细胞是。我们现在已经开发出一种新方法，可以轻松分离这些去分化上皮祖细胞的纯群体，并且我们将表征、培养和定义这些关键细胞的功能特性。最近发现了一种由 Gli1 表达定义的肾脏驻留间充质干细胞群，它代表纤维化疾病中的主要肌成纤维细胞前体群，这些细胞具有血管稳定特性，并且能够分化为周细胞和血管平滑肌细胞。这些细胞在体外和体内的功能，并将它们与内皮细胞和上皮细胞共培养，以在体外模拟肾小管间质。拟议的实验不仅将定义肾衰竭的新再生策略，还将验证两种关键的成体祖细胞群，这些细胞群将可用于治疗肾衰竭的各种再生方法。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Harnessing Expressed Single Nucleotide Variation and Single Cell RNA Sequencing To Define Immune Cell Chimerism in the Rejecting Kidney Transplant.

利用表达的单核苷酸变异和单细胞 RNA 测序来定义排斥性肾移植中的免疫细胞嵌合现象。

DOI：
发表时间：
2020-09
期刊：
影响因子：
0
作者：
Malone, Andrew F;Wu, Haojia;Fronick, Catrina;Fulton, Robert;Gaut, Joseph P;Humphreys, Benjamin D
通讯作者：
Humphreys, Benjamin D