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

使用体内溴脱氧尿苷（BrdU）标记，在正常成人肾脏中鉴定出肾小管细胞群（标记保留肾小管细胞[LRTC]），其积极促进损伤后肾脏的再生过程。在这里，这些LRTC的特点是在体外。通过FAGS从BrdU处理的大鼠肾脏中分离LRTC群体。LRTC和non-LRTC都经历了增殖，并在小管生成生长因子如EGF、TGF-α、IGF-I和肝细胞生长因子的存在下保持上皮表型。有趣的是，LRTC也增殖上皮标志物表达的可溶性因子的存在下，来自胚胎肾后肾间充质细胞系。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响应于已知在体外诱导肾细胞小管形成和/或参与体内肾再生的生长因子（肝细胞生长因子和成纤维细胞生长因子）而形成小管样或小管囊状结构。相反，非LRTC没有形成这些结构。当移植到后肾时，LRTC而不是非LRTC整合到肾单位的上皮成分中，包括近端小管细胞和输尿管芽。它们还分化成成纤维样细胞。总的来说，这些发现表明，LRTC是一个成年肾小管细胞群，显示表型可塑性，tubulogenic能力，并整合到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.