DEVELOPMENT OF HEPATIC SINUSOIDAL STRUCTURE WITH SPECIAL REFERENCE TOTHE ITO CELLS

To elucidate sinusoidal cell structure and function under normal condi tions and their behavior in diseased settings, an understanding of the ir developmental aspects is needed. At day 10 of gestation in mice and rats or at 5 weeks of gestation in humans, the hepatic cords grow int o the mesenchymal tissue of the septum transversum, and the primitive sinusoidlike structure is simultaneously observed between the liver ce ll cords. In the margin of the growing liver primordium, mesenchymal c ells in the septum transversum are trapped in the subendothelial space . These subendothelial cells are at the early stages of organogenesis and become progenitors of the Ito cells. By days 12-14 of gestation in mice and rats or 8 weeks of gestation in humans, the basic structure of the sinusoids has developed. Embryonic hepatic sinusoids are usuall y lined by a continuous endothelium without basement membranes, and an incompletely fenestrated sinusoid appears at the middle gestational s tage. In the late gestational stages, the Ito cells exhibit myofibrobl astlike features in humans, mice, and rats. In association with this e vent, perisinusoidal reticular networks are gradually intensified. Aft er birth until days 4-5 in mice and rats, the sinusoidal and perisinus oidal structures are almost completely formed, although slight morphol ogical differences from those in adult livers still exist. What happen s to sinusoidal endothelial cells and Ito cells in hepatic fibrosis-ci rrhosis of the adult may be a deviated or uncontrolled occurrence of w hat goes on during the fetal period, i.e., a continuous nonfenestrated sinusoidal lining in the early embryonic stage and a myofibroblastlik e transformation of Ito cells in late fetal life. (C) 1997 Wiley-Liss, Inc.