Regeneration of Glomerular Podocytes by Human Renal Progenitors
Regeneration of Glomerular Podocytes by Human Renal Progenitors
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DOI：
10.1681/asn.2008070709
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发表时间：
2009-02-01
影响因子：
13.6
通讯作者：
Romagnani, Paola
中科院分区：
文献类型：
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作者：
Ronconi, Elisa;Sagrinati, Costanza;Romagnani, Paola
肾小球疾病中常见的足细胞耗竭在肾小球硬化的发病机制中起着重要作用。成年期的足细胞损伤是否可以修复还没有确定。在这里，我们证明了在成人肾脏中，CD133+CD24+细胞由一组祖细胞组成，这些祖细胞在Bowman囊内以精确的顺序排列，并显示出异质性的分化和再生潜力。定位于尿极的细胞表达CD133和CD24，但不表达足细胞标志物(CD133+CD24+PDX-细胞)，可同时再生肾小管细胞和足细胞。相反，位于尿极和血管极之间的同时表达祖细胞和足细胞标志物(CD133+CD24+PDX+)的细胞只能再生足细胞。最后，定位于血管极的细胞没有表现出祖细胞标志，但表现出分化的足细胞(CD133-CD24-PDX+细胞)的表型特征。在阿霉素肾病小鼠体内注射CD133+CD24+PDX-细胞，但不注射CD133+CD24+PDX+或CD133-CD24-细胞，可减少蛋白尿并改善慢性肾小球损伤，提示CD133+CD24+PDX-细胞有可能治疗以足细胞损伤、蛋白尿和进行性肾小球硬化为特征的肾小球疾病。
Depletion of podocytes, common to glomerular diseases in general, plays a role in the pathogenesis of glomerulosclerosis. Whether podocyte injury in adulthood can be repaired has not been established. Here, we demonstrate that in the adult human kidney, CD133+CD24+ cells consist of a hierarchical population of progenitors that are arranged in a precise sequence within Bowman's capsule and exhibit heterogeneous potential for differentiation and regeneration. Cells localized to the urinary pole that expressed CD133 and CD24, but not podocyte markers (CD133+CD24+PDX- cells), could regenerate both tubular cells and podocytes. In contrast, cells localized between the urinary pole and vascular pole that expressed both progenitor and podocytes markers (CD133+CD24+PDX+) could regenerate only podocytes. Finally, cells localized to the vascular pole did not exhibit progenitor markers, but displayed phenotypic features of differentiated podocytes (CD133-CD24-PDX+ cells). Injection of CD133+CD24+PDX- cells, but not CD133+CD24+PDX+ or CD133-CD24- cells, into mice with adriamycin-induced nephropathy reduced proteinuria and improved chronic glomerular damage, suggesting that CD133+CD24+PDX- cells could potentially treat glomerular disorders characterized by podocyte injury, proteinuria, and progressive glomerulosclerosis.