Evolution of mesenchymal cells in fetal rat lung

Abstract

The evolution of connective tissue cells in the developing fetal rat lung is studied under the electron microscope from the 15th until the 21st day of gestation and is compared to the evolution of epithelial cells. Three successive types of stem cells ("mesocytoblasts") are present during the first stages of lung development studied (15 to 18 days of gestation). These stem cells appear to be able to differentiate into fibroblasts or into smooth muscle cells, according to their localization along the broncho-alveolar tubule. Myoblasts are situated near the bronchial epithelium, whereas fibroblasts occur under the alveolar epithelium. Epithelo-mesenchymal interactions are assumed to play a role in this differentiation process. Synthesis of both, collagen and elastic fibers and of cytoplasmic filaments by fibroblasts as well as by myoblasts reveal the multiple potentialities of the mesenchymal stem cell and suggest a common origin. The early fibroblast in characterized by long cytoplasmic processes which contain numerous cytofilaments, and by the presence of collagen fibers in the vicinity of the cell. Later on, (20 days of gestation) the mature fibroblast of the lung mesenchyme shows areas of RER, glycogen and lipidic vacuoles in its cytoplasm. Cytofilaments are numerous within very long cytoplasmic processes and elastic and collagen fibers are very frequent beside the cytoplasmic membrane. The earliest fibroblast differentiation occurs under the epithelium of primitive respiratory bronchioles, which indicate the limit between the bronchial and the alveolar territories. Later on, differentiating fibroblasts are found throughout the whole alveolar walls. Connective tissue cells other than mesenchymal stem cells, fibroblasts or myoblasts are observed during lung development. Vacuolar cells, similar to Hofbauer cells, transiently appear on the 16th day of gestation. On the 20th and the 21st day macrophage-like cells are present in the septal space of the alveolar wall. The absence of intermediate stages of differentiation and parallel evolution of blood cells suggest that those connective tissue cells are differentiated elsewhere and have then migrated from blood into lung mesenchyme. No cell death has been observed in the developing lung.

Development of macrophages in the lungs of fetal rabbits, rats, and hamsters

“…Hofbauer-like cells were also found in fetal rat lungs by Collet and Des Biens (1975), who saw them as transient cells of mesodermal origin in evidence only during days 16 and 17 of gestation and apparently unrelated to macrophages, which were not seen until days 20-21. In our interpretation, these cells are but one manifestation of the presence of rnacrophages and related forms that is continuous from the inception of pulmonary development.…”

The Effect of Corticosterone on the Growth of Perinatal Rat Lung Fibroblasts in Culture: Modulation by the Extracellular Matrix

“…Blood capillaries pervade the interstitium during this period (3,4), affording ample interaction between the fibroblasts and the endothelial matrix. Although fetal lung mitotic activity diminishes precipitously from day 17 to term (1, 15), the interstitial fibroblasts and the endothelial cells have been shown to be more mitotically active than the epithelium during the final two days of fetal lung development (I), when fetal corticosterone levels are still elevated (23).…”

“…In the developing rat lung, the interstitial fibroblasts undergo proliferative expansion at two intervals: the first occurs during fetal life, when peak mitotic activity of the mesenchymal stem cells is seen on day 16 (term=day 23) (1,4,15); the second occurs during postnatal life, from the fourth ~ through thirteenth days after birth, during which period the differentiated fibroblasts actively engage in the septation process (1 1 I 22). The fetal and postnatal intervals of fibroblast expansion are each followed by a sharp decline in mitotic activity (1, 1 1, 15), which, interestingly, coincides temporally with the fetal (23) and postnatal (9, 14) bursts in corticosterone secretion.…”

Fibroblasts and myofibroblasts

“…The pattern of airway branching is dependent on the interactions between the developing mesenchyme, epithelial cells, cellular adhesion molecules and the extracellular matrix, in particular, proteoglycans and glycosaminoglycans [74]. In the developing lungs of rats, the differentiation of mesenchymal stem cells into fibroblasts-like and myofibroblast-like cells is associated with the production and deposition of extracellular matrix molecules [75]. The deposition of collagen, syndecan, laminin and fibronectin from these cells is essential for airway morphogenesis, in particular tubule formation and terminal branching [65,73,76].…”