Identification and characterization of renal progenitor-like tubular cells that participate in the regeneration processes of the kidney

利用体内溴脱氧尿苷（BrdU）标记技术，在正常成人肾脏中发现了一个小管细胞群（标签保留小管细胞[LRTC]），它对损伤后肾脏的再生过程起着积极的作用。在这里，这些LRTC在体外被表征。用FAGS从brdu处理的大鼠肾脏中分离出LRTC群体。在小管生长因子如EGF、TGF-α、IGF-I和肝细胞生长因子存在的情况下，LRTC和非LRTC均发生增殖并维持上皮表型。有趣的是，来自胚胎肾后肾间充质细胞系的可溶性因子存在时，LRTC也在没有上皮标记物表达的情况下增殖。细胞外基质的类型强烈影响LRTC的表型。此外，在三维胶原凝胶培养中，LRTC在生长因子（肝细胞生长因子和成纤维细胞生长因子）的作用下形成小管样或小管囊结构，这些生长因子已知在体外诱导肾细胞小管形成和/或参与体内肾再生。相比之下，非lrtc不形成这些结构。当移植到后肾时，LRTC而非LRTC被整合到肾元的上皮成分中，包括近端小管细胞和输尿管芽。它们也分化为成纤维细胞样细胞。总的来说，这些发现表明LRTC是一种成人肾小管细胞群，具有表型可塑性、小管形成能力和融入发育中的肾脏的能力。

Using in vivo bromodeoxyuridine (BrdU) labeling, a tubular cell population (label-retaining tubular cells [LRTC]) was identified in normal adult kidneys, which contributes actively to the regeneration process of the kidney after injury. Here, these LRTC are characterized in vitro. The LRTC population was isolated from BrdU-treated rat kidney by FAGS. Both LRTC and non-LRTC underwent proliferation and maintained an epithelial phenotype in the presence of tubulogenic growth factors such as EGF, TGF-α, IGF-I, and hepatocyte growth factor. It is interesting that LRTC also proliferated without epithelial markers expression in the presence of soluble factors derived from an embryonic kidney metanephric mesenchyme cell line. The type of extracellular matrix strongly influenced the phenotype of LRTC. Furthermore, in three-dimensional collagen gel culture, LRTC formed tubule-like or tubulocystic structures in response to growth factors (hepatocyte growth factor and fibroblast growth factor) that are known to induce kidney cell tubulogenesis in vitro and/or participate in renal regeneration in vivo. In contrast, non-LRTC did not form these structures. When transplanted into the metanephric kidney, LRTC but not non-LRTC were integrated into epithelial components of nephron, including the proximal tubular cells and the ureteric bud. They also differentiated into fibroblast-like cells. Collectively, these findings suggest that LRTC are an adult kidney tubular cell population that shows phenotypic plasticity, tubulogenic capacity, and integration capability into the developing kidney.