Characterization of Renal Progenitors Committed Toward Tubular Lineage and Their Regenerative Potential in Renal Tubular Injury
Characterization of Renal Progenitors Committed Toward Tubular Lineage and Their Regenerative Potential in Renal Tubular Injury
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DOI：
10.1002/stem.1130
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发表时间：
2012-08-01
期刊：
影响因子：
5.2
通讯作者：
Romagnani, Paola
中科院分区：
文献类型：
--
作者：
Angelotti, Maria Lucia;Ronconi, Elisa;Romagnani, Paola
最近的研究表明，成人肾脏中存在一群具有再生肾小球和肾小管上皮细胞潜力的肾祖细胞，其特征在于表面标志物CD 133和CD 24的共表达。在这里，我们证明，CD 133 + CD 24+肾祖细胞可以区分不同的亚群从正常人肾脏血管细胞粘附分子1，也称为CD 106的表面表达的基础上。CD 133 + CD 24 + CD 106+细胞定位于Bowman囊的尿极，而分散的CD 133 + CD 24 + CD 106-细胞的独特群体定位于近曲小管以及远曲小管。CD 133 + CD 24 + CD 106+细胞具有较高的增殖率，并可向足细胞和肾小管细胞分化。相比之下，CD 133 + CD 24 + CD 106-细胞表现出较低的增殖能力，并显示出朝向肾小管谱系的定型表型。与肾脏的所有其他分化细胞相比，CD 133 + CD 24 + CD 106+和CD 133 + CD 24 + CD 106-细胞均显示出对有害物质的更高抗性。一旦注射到受急性肾小管损伤影响的SCID小鼠中，这两个群体都显示出在肾脏内移植、产生新的肾小管细胞和改善肾功能的能力。这些特性是成人肾脏的其他肾小管细胞所不具备的。最后，CD 133 + CD 24 + CD 106-细胞在肾小管损伤后增殖，成为急性或慢性肾小管损伤患者再生上皮的主要部分。这些数据表明，CD 133 + CD 24 + CD 106-细胞代表肾小管定向祖细胞，其显示出对凋亡刺激的抗性，并对受损的肾小管组织发挥再生潜力。干细胞2012;30：1714-1725
Recent studies implicated the existence in adult human kidney of a population of renal progenitors with the potential to regenerate glomerular as well as tubular epithelial cells and characterized by coexpression of surface markers CD133 and CD24. Here, we demonstrate that CD133+CD24+ renal progenitors can be distinguished in distinct subpopulations from normal human kidneys based on the surface expression of vascular cell adhesion molecule 1, also known as CD106. CD133+CD24+CD106+ cells were localized at the urinary pole of Bowman's capsule, while a distinct population of scattered CD133+CD24+CD106- cells was localized in the proximal tubule as well as in the distal convoluted tubule. CD133+CD24+CD106+ cells exhibited a high proliferative rate and could differentiate toward the podocyte as well as the tubular lineage. By contrast, CD133+CD24+CD106- cells showed a lower proliferative capacity and displayed a committed phenotype toward the tubular lineage. Both CD133+CD24+CD106+ and CD133+CD24+CD106- cells showed higher resistance to injurious agents in comparison to all other differentiated cells of the kidney. Once injected in SCID mice affected by acute tubular injury, both of these populations displayed the capacity to engraft within the kidney, generate novel tubular cells, and improve renal function. These properties were not shared by other tubular cells of the adult kidney. Finally, CD133+CD24+CD106- cells proliferated upon tubular injury, becoming the predominating part of the regenerating epithelium in patients with acute or chronic tubular damage. These data suggest that CD133+CD24+CD106- cells represent tubular-committed progenitors that display resistance to apoptotic stimuli and exert regenerative potential for injured tubular tissue. STEM CELLS 2012;30:1714-1725