Regenerative Medicine of Nephron Segments

缺血性急性肾功能衰竭(ARF)是成人中最常见的ARF形式。肾缺血损伤后肾小管再生的分子机制仍不清楚。有人认为，再生过程可能会重现发育过程，以恢复器官或组织的功能。成年肾小管上皮细胞在细胞损伤后具有较强的再生能力。我们研究了两个发育基因WNT-4和Ets-1在ARF肾小管再生中的功能作用。这张幻灯片显示了肾小管再生机制的假说。肾小管缺血等肾小管损伤后，肾小管细胞发生凋亡或坏死。然后，受损肾小管的某些部分会再生。我们假设有三种可能的肾小管再生。其一是肾小管干细胞的存在。关于干细胞，在这次会议上已经报道了Mamy的陈述。第二种可能性是去分化。我们的假设是肾小管上皮细胞向去分化细胞转化，去分化细胞具有胚胎特征，如表达WNT-4和Ets-1。另一种可能性是血细胞的参与。综上所述，我们证明了当肾小管细胞受损时，使用多种类型的干细胞可以实现几种修复机制。我们可以通过操纵干细胞来促进肾小管损伤的恢复，如组织特异性干细胞，或去分化干细胞，骨髓源性干细胞，或ES细胞。对肾脏再生的进一步认识将促进ARF的新的治疗策略。

Ischemic acute renal failure (ARF) is the most common form of ARF in the adult population. The molecular mechanisms of tubular regeneration after ischemic renal injury remain largely unknown. It has been suggested that regeneration processes may recapitulate developmental processes in order to restore organ or tissue function. The adult tubular epithelial cells have a potent ability of regenerate after cellular damage. We examined functional role of two developmental genes, Wnt-4 and Ets-1 in renal tubular regeneration in ARF. This slide shows hypothesis of mechanisms of renal tubular regeneration. After renal tubular injury, such as ischemia, renal tubular cells falls into apoptosis or necrosis. Then, some parts of injured renal tubules regenerate. We hypothesized three possibilities of renal tubular regeneration. One is the presence of renal tubular stem cells. Concerning to the stem cells, mamy presentation have already been reported in this meeting. The second possibility is Dedifferentiation. Our hypothesis is that the renal tubular cells transform to dedifferentiated cells, which have embryonic character, such as expression of Wnt-4 and Ets-1. The other possibility is involvement of blood cells.In summary, we demonstrated that when the renal tubular cells are damaged, several recovery mechanisms are occurs using many types of stem cells. We may improve the recovery of renal tubular damage by manipulating stem cells such as tissue specific stem cells, or dedifferentiated stem cells, bone-marrow deribed stein cells, or ES cells. Further understanding of renal regeneration will improve new therapeutic strategy for ARF.