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Kidney Progenitor Cells in Disease

疾病中的肾脏祖细胞

基本信息

批准号：
8268567
负责人：
KENNETH W GROSS
金额：
$ 53.34万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2014-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Understanding normal mechanisms of kidney regeneration in response to injuries is of vital importance to developing new therapies to tackle the increasing burden of chronic kidney disease and organ failure. Although the adult mammalian kidney lacks nephron progenitors that could regenerate entire nephrons, nevertheless it has remarkable capacity to regenerate. Recent studies have focused predominantly on tubule regeneration, yet have failed to identify an epithelial progenitor cell in adult kidney. However, there has been little attention to the vasculature. The overall goal of this application is to identify and study adult kidney quiescent stem/progenitor cells. Accordingly, a team of four experts has come together bringing unique backgrounds and skills including stem cell biology. Renin cell biology, kidney development, glomerular and interstitial injuries, and Regenerative Medicine specifically identify and characterize latent progenitors lying within the kidney. In exciting new feasibility studies using unique genetic tools, these investigators have shown evidence of recent collaborations by identifying putative latent progenitor cells that are activated in response to kidney injuries and growth. These cells yield progeny that repopulate vascular mural cells of the glomerulus (podocytes) and interstitium (pericytes and endothelial cells). In the first year of this R24 application (Phase I, addressed here) the investigators plan to establish irrefutably the presence and capacity of these latent progenitors using two distinct but complementary state-of-the-art fate mapping techniques in kidneys. Assuming the success of Phase I, the Investigators will then propose Phase II (years 2-5 of the R24 application) in which they will methodically dissect how these progenitors are activated, what lineal restrictions exist in the progeny of these progenitors, study their capacity in aging, and attempt to harness these progenitors to promote kidney cell regeneration. PUBLIC HEALTH RELEVANCE: Acute Kidney Injury, Chronic Kidney Disease and End Stage Kidney Disease are major health burdens. Understanding how the kidney regenerates in response to injuries is vital to generating new therapies that will prevent or limit the developmen of chronic kidney disease or end stage kidney disease. These initial studies will study progenitor cells in the adult kidney that have the capacity to generate new kidney cells, particularly of the blood vessels of the kidney. The investigators will determine how important these progenitors are in regeneration after kidney damage.

描述（由申请人提供）：了解损伤后肾脏再生的正常机制对于开发新的治疗方法来解决慢性肾脏疾病和器官衰竭日益增加的负担至关重要。尽管成年哺乳动物肾脏缺乏能够再生整个肾元的肾元祖细胞，但它具有显著的再生能力。最近的研究主要集中在小管再生上，但未能在成人肾脏中鉴定上皮祖细胞。然而，很少有人关注血管系统。总的目标是