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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.