Identification of tubular epithelial stem cells and their roles on recovery from acute renal failure

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Initially regenerating cells in uranyl acetae-induced acute renal failure was investigated in relation to the epithelial stem cells. The findings are as follows.1)Initially regenerating cells regardless of degrees of injury in S3 segment by different doses of uranyl acetate injection are dedifferentiated pre-existing mature proximal tubular cells, which may be responsible for focal repair of S3.2)Initially regenerating cells showed 3H-thymidine label-retaining, and cells in the distal S3 even after contributing to renewal of the entire S3 were identified as label retaining cells for about 6 weeks.3)Initially regenerating cells in the distal S3 showed a large capacity for proliferation and ability to produce daughter cells capable for the repair of entire S3.4)Daughter (proliferating) cells of initially regenerating cells may die from 5-fluorouracil (FU) treatment, while initially regenerating cells in the distal S3 were 5-FU resistant and confined there. After stopping 5-FU, those cells proliferated toward the proximal direction of S3 with showing mature proximal tubular phenotype.The findings indicate that initially regenerating PT cells in the distal S3 show slow cycling under steady condition, a large capacity for proliferation. ability to produce daughter cells capable for the repair of entire S3. and 5-FU resistant, suggesting that some PT cells in the distal S3 might be a stem/progenitor cell population in S3 segment of proximal tubule. In addition, the cells may exist in a location between S3 and the thin descending limb of Henle, where might be stern cell niche. Further analysis of the cells in the distal S3 in relation to epithelial stem cells would contribute to development of new therapeutic strategy for acute renal failure.