Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, SUS Malmö, Malmö, Sweden.
Am J Pathol. 2011 Feb;178(2):828-37. doi: 10.1016/j.ajpath.2010.10.026.
The tubules of the kidney display a remarkable capacity for self-renewal on damage. Whether this regeneration is mediated by dedifferentiating surviving cells or, as recently suggested, by stem cells has not been unequivocally settled. Herein, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDH(high) and ALDH(low) cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population scattered through the proximal tubules (PTs). These cells expressed CD24 and CD133, previously described markers for renal progenitors of Bowman's capsule. Furthermore, we show that the PT cells, and the glomerular progenitors, are positive for KRT7, KRT19, BCL2, and vimentin. In addition, tubular epithelium regenerating on acute tubular necrosis displayed long stretches of CD133(+)/VIM(+) cells, further substantiating that these cells may represent a progenitor cell population. Furthermore, a potential association of these progenitor cells with papillary renal cell carcinoma was discovered. Taken together, our data demonstrate the presence of a previously unappreciated subset of the PT cells that may be endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules.
肾脏的小管显示出在损伤后自我更新的显著能力。这种再生是由去分化的存活细胞介导的,还是最近提出的由干细胞介导的,尚未明确解决。在此,我们证明醛脱氢酶(ALDH)活性可用于从成人肾皮质组织中分离具有祖细胞特征的细胞。对分离的 ALDH(high)和 ALDH(low)细胞部分进行基因表达谱分析,然后对肾组织进行免疫组织化学检测,使我们能够描绘出散布在近端小管(PT)中的暂定祖细胞群。这些细胞表达 CD24 和 CD133,这是以前描述的鲍曼囊肾祖细胞的标志物。此外,我们表明 PT 细胞和肾小球祖细胞对 KRT7、KRT19、BCL2 和波形蛋白呈阳性。此外,在急性肾小管坏死中再生的肾小管上皮细胞显示出长段的 CD133(+)/VIM(+)细胞,进一步证实这些细胞可能代表祖细胞群。此外,还发现这些祖细胞与乳头状肾细胞癌之间存在潜在的关联。总之,我们的数据表明,PT 细胞中存在以前未被认识到的亚群,这些细胞可能具有更强的表型,能够提高对急性肾损伤的抵抗力,从而能够快速重新填充肾小管。