Pathways of differentiation of airway epithelial cells.

The question being examined is whether one or more morphologically distinct cell types can be identified in the conducting airways of adult rabbits possessing stem cell functions. The term "stem cell" is used to denote cells with extensive self-replicating potential and the ability to produce differentiated progeny. According to various models of cell renewal in the conducting airways that have been proposed over the years, two different cell types have to be regarded as primary candidates for the stem cell: basal cells and some type of secretory cells. The question is complicated by the fact that significant differences exist between species in the distribution and morphological characteristics of airway cell types. In addition, different airway segments may or may not be occupied by different populations of stem cells. Previously, investigators have addressed the problem by studying normal cell regeneration or injury induced cell regeneration in vivo in the whole animal. We decided to attempt a different approach, namely, to separate specific cell types and to study the proliferation and differentiation capacity of such cell isolates using in vitro and in vivo cell culture techniques. Our studies lead us to conclude that the conducting airways of adult rabbits contain at least two distinct cell populations endowed with stem cell potential, namely basal cells and bronchiolar Clara cells. From that it follows that the trachea and bronchi, on one hand, and the bronchioles, on the other hand, are occupied by two different stem cell populations governing renewal of the epithelial lining.