Adult Progenitors in Kidney Tubulointerstitium

 描述（由申请人提供）：肾衰竭在美国是一个严重的健康问题，它反映了肾单位修复失败和进行性纤维化的后果。治疗肾功能衰竭的两个有前途的策略包括功能性肾单位的体内再生和可移植肾单位的体外工程化。我们已经确定了两个关键的成人肾祖细胞群体具有强大的潜力，发挥重要作用，在每一个战略。在肾小管内，我们以前已经表明，去分化的近端小管细胞负责修复近端小管的增殖扩张。我们现在已经产生了一种新的方法来容易地分离这些去分化的上皮祖细胞的纯群体，我们将表征，培养和定义这些关键细胞的功能特性。另外我们 最近鉴定了一种由Gli1表达定义的肾驻留间充质干细胞群，其代表纤维化疾病中主要的肌成纤维细胞前体群。这些细胞具有血管稳定特性，并且能够分化成周细胞和血管平滑肌细胞。我们将进一步在体外和体内研究这些细胞的功能，并将它们与内皮细胞和上皮细胞共培养，以建立体外肾小管上皮细胞模型。总之，拟议的实验不仅将定义新的再生策略，肾衰竭，但也将验证两个关键的成人祖细胞群体，将是有用的各种再生方法来治疗肾衰竭。

 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.