In vitro-toxicology

Before chemicals and pharmaceuticals can enter the market they have to be tested for potential adverse effects on human health. Usually, such investigations are performed using mice and rats, but also other animal species are used in toxicity testing, e.g., dogs and primates. Apart from ethical concerns animal experiments are characterized by problems with regard do the limited predicitvity for human biology. Prominent examples are thalidomide and the monoclonal antibody TGN1412 which passed toxicity testing in animals but led to serious adverse effects in humans. Therefore, an urgent need for new approaches on the basis of human cells and tissues, representing human biology better than animal models, is existing in toxicology.

The placenta in toxicology

The placenta is a complex organ which is responsible for the feto-maternal exchange, but also plays a central role in the maintenance of pregnancy or protecting the fetus against the maternal immune system. In addition to placenta-specific trophoblasts with importance for substance transfer across the placental barrier, the placenta contains a range of further cell types, for example different kinds of immune cells, fibroblasts, stem cells or endothelial cells.

At the same time, the placenta is the only organ of humans which is permanently available for research in a healthy condition. The complexity in combination with the fact that the placenta or tissue explants stay vital for a longer period of time after delivery, makes it a perfect model for human toxicity testing. Apart from the field of general toxicity testing the placenta, amongst others, can be used for immunotoxicity, reproductive toxicity, the analysis of substances affecting the hormone system and toxic effects or transfer of nanoparticles.

In contrast to other in-vitro-models the placenta combines the following advantages

• all cells are primary cells of human origin
• all cells are located in their natural environment, important for cell-cell-interactions (e.g., between immune cells and endothelial cells)
• the placenta is permanently available
• the placenta is a healthy organ which is not coined by pathological processes which could influence the experimental results in toxicity testing
• numerous parameters can be measured at the same time point, for example cytokine release of immune cells and hormone production of trophoblasts
• placental tissue explants can be cultivated with autologues blood which could be of significance when substances are bound to serum proteins

The toxicological placenta cascade

The placenta offers the opportunity to analyze chemicals and pharmaceuticals in a cascade of increasing complexity. The first steps of the cascade are characterized by low costs and and time consumption and can be used for identifying toxic substances early. The later steps are more complex and serve the toxicological analysis of substances which passed the first steps without obvious toxic effects.