Hepatic microvascular development in relation to the morphogenesis of hepatocellular plates in neonatal rats

Abstract

The development of hepatic microvascular heterogeneity after birth, and its temporal relationship to the development of parenchymal cell plates have received little attention. As a result, the morphogenesis of some of the parameters contributing to this heterogeneity in suckling and weaned rats was studied as a function of time between postpartum days 4 and 30 using in vivo light microscopic, electron microscopic, and immunocytochemical methods. During the early suckling period, the sinusoid network is highly anastomotic, with little evidence of zonation, and the parenchymal cell plates contain multiple cells and are irregularly arranged throughout the lobule. Sinusoidal endothelial fenestration is sparse at 4 days, but phagocytic Kupffer cell (KC) function already exists and exhibits zonal heterogeneity, with more cells located in the periportal zone. With increasing age, endothelial fenestrae increase and organize as sieve plates. Widened centrilobular radial sinusoids form through a loss ("drop-out") of intersinusoidal sinusoids (ISS). Concomitantly, the associated cell plates straighten and become one cell thick. Hepatocyte DNA synthesis and mitosis are higher in the periportal zone, which retains thickened cell plates and anastomotic sinusoids. The centrilobular sinusoids may widen to accommodate the increased volume of blood that results from the loss of ISS as well as the increased numbers of periportal sinusoids containing flow that feed these vessels. KC phagocytic activity increases during the suckling period concomitant with an increase of gut-derived endotoxin in the portal blood, which suggests that the KCs may be releasing mediators that affect sinusoid diameter, blood flow, endothelial fenestration, and perhaps parenchymal growth either directly or through the stimulation of growth factors.

Intestinal Microcirculatory Dysfunction During the Development of Experimental Necrotizing Enterocolitis

“…At 0, 2, 3, and 4 d, animals were anesthetized with an s.c. injection of a mixture of ketamine (100 mg/kg) and xylazine (10 mg/kg). The intestinal microvascular responses were examined using established high resolution in vivo microscopic methods (18,19). Briefly, a compound binocular microscope (Leitz, Wetzlar, Germany) adapted for in vivo microscopy was equipped to provide either transillumination or epi-illumination as well as video microscopy using a charge-coupled device camera (MTI, Michigan City, IN).…”

The quest for liver progenitor cells: A practical point of view

“…The particular zonation of hepatocytes purges the vicinity of LPCs from high excess of exogenous but also endogenous molecules. The organization of the sinusoidal framework displays heterogeneity throughout the length of the sinusoid, simultaneously on the size, the number and the distribution of the fenestrae, but also on the infrastructure of the sinusoids network [69,95,158,162,163].…”

Laser-guided direct writing for three-dimensional tissue engineering

“…It is important to note that the space of Disse has not formed, suggesting these structures are not fully developed sinusoids. However, several studies suggest that the space of Disse forms between 4 and 12 weeks after liver development in vivo (Couvelard et al, 1996;McCuskey et al, 2003), our cultures might follow a similar differentiation path. In addition to ultrastructural analysis our results show that sinusoid-like structures retain cytochrome P450 gene expression and activity as well as stable albumin gene expression and secretion for over 2 months in vitro (Nahmias et al, 2005).…”