Prenatal origins of human intrapulmonary arteries formation and smooth muscle maturation

Recent studies on the morphogenesis of the pulmonary arteries have focused on nonhuman species such as the chick and the mouse. Using immunohistochemi cal techniques, we have studied 16 lungs from human embryos and fetuses fro m 28 d of gestation to newborn, using serial sections stained with a panel of antibodies specific for endothelium, smooth muscle, and extracellular ma trix proteins. Cell replication was also assessed. Serial reconstruction sh owed a continuity of circulation between the heart and the capillary plexus from at least 38 d of gestation, The intrapulmonary arteries appeared to b e derived from a continuous expansion of the primary capillary plexus that is from within the mesenchyme, by vasculogenesis, The arteries formed by co ntinuous coalescence of endothelial tubes alongside the newly formed airway . Findings were consistent with the pulmonary arterial smooth muscle cells being derived from three sites in a temporally distinct sequence: the earli est from the bronchial smooth muscle, later from the mesenchyme surrounding the arteries, and last from the endothelial cells. Despite their different origins, all smooth muscle cells followed the same sequence of expression of smooth muscle-specific cytoskeletal proteins with increasing age. The or der of appearance of these maturing proteins was from the subendothelial ce lls outward across the vessel wall and from hilum to periphery. The airways would seem to act as a template for pulmonary artery development. This stu dy provides a framework for studying the signaling mechanisms controlling t he various aspects of lung development.