Lung - Regeneration

Regeneration is the process whereby denuded portions of epithelium-lined surfaces (i.e., airways and alveoli) are repaired. Once the epithelium becomes necrotic or ulcerated, the adjacent, viable epithelial cells replace the lost cells. In the airways, the process begins with elongation of the adjacent epithelial cells, which become flattened, and migration of these cells across the wound to cover the basement membrane (Figure 1 and Figure 2). In later stages, the epithelium begins to proliferate to replace the lost cells to return the epithelial lining to its normal state. In the alveoli, the type II pneumocytes are the progenitor cells and undergo these processes to replace lost alveolar type I cells. In some cases, the regenerating epithelium may overshoot the normal number of epithelial cells and become hyperplastic (Figure 3). In such cases, in the absence of recognizable necrosis or ulceration, it may be difficult to determine whether the hyperplasia is due to regeneration or is a primary response to test article exposure. For this reason, the term "regeneration" is reserved for those cases where there is evidence of epithelial damage. Other features of regeneration may include characteristics consistent with cellular proliferation, such as karyomegaly and cytomegaly. Additionally, the proliferating cells may have a slightly atypical appearance, so the pathologist may need to distinguish between regeneration and cellular atypia.