Study of tracheal regeneration after injury induced by 5-fluorouracil in rats

Abstract

Localization of tracheal stem cells in rat trachea. Extracorporeal tracheal injury (Wistar rats) was induced by 5-FU. The process of regeneration was observed and analyzed by light microscopy, electron microscopy, and immunohistochemistry. Twelve hours after treatment with 5-FU, the tracheal epithelium shed and cells with naked nuclei were seen located sparsely on the basement membrane. Six hours after removal of 5-FU, the tracheal rings were covered with flattened epithelium. These cells were poorly differentiated under electron microscopy. Immunohistochemistry showed few proliferating cell nuclear antigen (PCNA)-negative cells sparsely scattered among PCNA-positive cells on the basement membrane. Nine hours later, electron microscopy found that these cells differentiated into mucous cells and ciliated cells. Forty-eight hours later, the tracheal rings were entirely covered by pseudostratified ciliated columnar epithelium. A small number of G(0) cells with naked nuclei are located sparsely on the basement membrane of the trachea. Tracheal epithelium regenerates by proliferation and differentiation of these cells. It is likely that some of these G(0) cells on the tracheal basement membrane represent tracheal stem cells.