50 research outputs found
Dendritic polyglycerol nanoparticles show charge dependent bio-distribution in early human placental explants and reduce hCG secretion
A thorough understanding of nanoparticle bio-distribution at the feto-maternal
interface will be a prerequisite for their diagnostic or therapeutic
application in women of childbearing age and for teratologic risk assessment.
Therefore, the tissue interaction of biocompatible dendritic polyglycerol
nanoparticles (dPG-NPs) with first- trimester human placental explants were
analyzed and compared to less sophisticated trophoblast-cell based models.
First-trimester human placental explants, BeWo cells and primary trophoblast
cells from human term placenta were exposed to fluorescence labeled, ∼5 nm
dPG-NPs, with differently charged surfaces, at concentrations of 1 µM and 10
nM, for 6 and 24 h. Accumulation of dPGs was visualized by fluorescence
microscopy. To assess the impact of dPG-NP on trophoblast integrity and
endocrine function, LDH, and hCG releases were measured. A dose- and charge-
dependent accumulation of dPG-NPs was observed at the early placental barrier
and in cell lines, with positive dPG-NP-surface causing deposits even in the
mesenchymal core of the placental villi. No signs of plasma membrane damage
could be detected. After 24 h we observed a significant reduction of hCG
secretion in placental explants, without significant changes in trophoblast
apoptosis, at low concentrations of charged dPG-NPs. In conclusion, dPG-NP’s
surface charge substantially influences their bio-distribution at the feto-
maternal interface, with positive charge facilitating trans-trophoblast
passage, and in contrast to more artificial models, the first-trimester
placental explant culture model reveals potentially hazardous influences of
charged dPG-NPs on early placental physiology
A New Method for Morphometric Analysis of Tissue Distribution of Mobile Cells in Relation to Immobile Tissue Structures
The distribution of cells in stained tissue sections provides information that may be analyzed by means of morphometric computation. We developed an algorithm for automated analysis for the purpose of answering questions pertaining to the relative densities of wandering cells in the vicinity of comparatively immobile tissue structures such as vessels or tumors. As an example, we present the analysis of distribution of CD56-positive cells and of CXCR3-positive cells (relative densities of peri-vascular versus non-vascular cell populations) in relation to the endothelium of capillaries and venules of human parietal decidua tissue of first trimester pregnancy. In addition, the distibution of CD56-positive cells (mostly uterine NK cells) in relation to spiral arteries is analyzed. The image analysis is based on microphotographs of two-color immunohistological stainings. Discrete distances (10–50 µm) from the fixed structures were chosen for the purpose of definining the extent of neighborhood areas. For the sake of better comparison of cell distributions at different overall cell densities a model of random distribution of “cells” in relation to neighborhood areas and rest decidua of a specific sample was built. In the chosen instances, we found increased perivascular density of CD56-positive cells and of CXCR3-positive cells. In contrast, no accumulation of CD56-positive cells was found in the neighborhood of spiral arteries