An advanced human in vitro co-culture model for translocation studies across the placental barrier.

Although various drugs, environmental pollutants and nanoparticles (NP) can cross the human placental barrier and may harm the developing fetus, knowledge on predictive placental transfer rates and the underlying transport pathways is mostly lacking. Current available in vitro placental transfer models are often inappropriate for translocation studies of macromolecules or NPs and do not consider barrier function of placental endothelial cells (EC). Therefore, we developed a human placental in vitro co-culture transfer model with tight layers of trophoblasts (BeWo b30) and placental microvascular ECs (HPEC-A2) on a low-absorbing, 3 µm porous membrane. Translocation studies with four model substances and two polystyrene (PS) NPs across the individual and co-culture layers revealed that for most of these compounds, the trophoblast and the EC layer both demonstrate similar, but not additive, retention capacity. Only the paracellular marker Na-F was substantially more retained by the BeWo layer. Furthermore, simple shaking, which is often applied to mimic placental perfusion, did not alter translocation kinetics compared to static exposure. In conclusion, we developed a novel placental co-culture model, which provides predictive values for translocation of a broad variety of molecules and NPs and enables valuable mechanistic investigations on cell type-specific placental barrier function.

Impact of particle size and surface modification on gold nanoparticle penetration into human placental microtissues.

AIM: Nanoparticle-based drug carriers hold great promise for the development of targeted therapies in pregnancy with reduced off-target effects. Here, we performed a mechanistic in vitro study on placental localization and penetration of gold nanoparticles (AuNPs) in dependence of particle size and surface modification. MATERIALS & METHODS: AuNP uptake and penetration in human placental coculture microtissues was assessed by inductively coupled plasma-mass spectrometry, transmission electron microscopy and laser ablation-inductively coupled plasma-mass spectrometry. RESULTS: Higher uptake and deeper penetration was observed for smaller (3-4 nm) or sodium carboxylate-modified AuNPs than for larger (13-14 nm) or PEGylate AuNPs, which barely passed the trophoblast barrier layer. CONCLUSION: It is possible to steer placental uptake and penetration of AuNPs by tailoring their properties, which is a prerequisite for the development of targeted therapies in pregnancy.

A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment.

There is increasing evidence that certain nanoparticles (NPs) can overcome the placental barrier, raising concerns on potential adverse effects on the growing fetus. But even in the absence of placental transfer, NPs may pose a risk to proper fetal development if they interfere with the viability and functionality of the placental tissue. The effects of NPs on the human placenta are not well studied or understood, and predictive in vitro placenta models to achieve mechanistic insights on NP-placenta interactions are essentially lacking. Using the scaffold-free hanging drop technology, we developed a well-organized and highly reproducible 3D co-culture microtissue (MT) model consisting of a core of placental fibroblasts surrounded by a trophoblast cell layer, which resembles the structure of the in vivo placental tissue. We could show that secretion levels of human chorionic gonadotropin (hCG) were significantly higher in 3D than in 2D cell cultures, which indicates an enhanced differentiation of trophoblasts grown on 3D MTs. NP toxicity assessment revealed that cadmium telluride (CdTe) and copper oxide (CuO) NPs but not titanium dioxide (TiO2) NPs decreased MT viability and reduced the release of hCG. NP acute toxicity was significantly reduced in 3D co-culture MTs compared to 2D monocultures. Taken together, 3D placental MTs provide a new and promising model for the fast generation of tissue-relevant acute NP toxicity data, which are indispensable for the safe development of NPs for industrial, commercial and medical applications.

Nanoparticle transport across the placental barrier: pushing the field forward!

The human placenta is a multifunctional organ constituting the barrier between maternal and fetal tissues. Nanoparticles can cross the placental barrier, and there is increasing evidence that the extent of transfer is dependent on particle characteristics and functionalization. While translocated particles may pose risks to the growing fetus particles may also be engineered to enable new particle-based therapies in pregnancy. In both cases, a comprehensive understanding of nanoparticle uptake, accumulation and translocation is indispensable and requires predictive placental transfer models. We examine and evaluate the current literature to draw first conclusions on the possibility to steer translocation of nanoparticles. In addition, we discuss if current placental models are suitable for nanoparticle transfer studies and suggest strategies to improve their predictability.

Packaging--a problem for patients with hand disorders? A cross-sectional study on the forces applied to packaging tear tabs.

INTRODUCTION: Patients with hand disorders frequently experience difficulties opening peelable packaging. PURPOSE: To investigate the forces patients can apply to tear tabs and to compare the results with normative data to make recommendations for the industry and clinical practice. STUDY DESIGN: Descriptive, cross-sectional. METHODS: One hundred patients with hand disorders were studied. The pinch pull force (PPF) applied to tear tabs of different lengths and materials (aluminum, plastic) was measured with a specially designed device. Key pinch was measured with a pinch gauge. Normative data were taken from another study on 402 healthy adults. RESULTS: Patients were able to apply most force to the longest aluminum tab, using the key grip, but this was only 53% of the force exerted by healthy people. Key pinch determines PPF (R(2)=0.548, p≤0.001). CONCLUSIONS: Manufacturers should provide long aluminum tear tabs. Health professionals are encouraged to measure key pinch to detect difficulties in opening packages. LEVEL OF EVIDENCE: Level IV.