Organoids and 3D-cultures for the toxicologic analysis of potentielly harmful substances

Whether it's food and drink, medication, or environmental contaminants – everything that enters the body can affect its various organ systems. Ingesting toxic substances can damage organs or impair their function. The gastrointestinal tract, as the entry point into the body and a barrier, the liver as an energy store and detoxification organ, and the thyroid gland as a producer of vital hormones can all be significantly affected.

Currently, many in vivo (in the body) animal studies are still conducted to investigate potentially harmful substances. As an alternative, three-dimensional growing in vitro (in test tube) methods are being developed. 3D cell cultures, such as organoids, make it possible to replicate organ-like functions in the laboratory. This allows the toxicity of chemicals to be tested in a system that adequately simulates the physiological response of the organ. At the Bf3R, organoids and 3D cultures are being established as modern toxicological analysis platforms that will be used in the future as standardized alternatives to animal testing.

Organoids are three-dimensional in vitro cultures that can be grown from stem cells or tissue cells extracted from various organs. They form complex structures that more closely resemble the respective organ in form and function than conventional cell cultures. Defined culture conditions enable cell growth and self-organization, as well as the formation of organ-specific cell types, while a portion of the stem cell population is retained. In this way, the different functions of organs can be replicated in vitro – including their response to toxic substances. Organoids thus represent a controllable tool for investigating the effects of substances in an in vivo-like culture.

One goal of the Bf3R is to develop and standardize 3D in vitro models for toxicological analyses and to implement them as an alternative method to animal testing.

Particular emphasis is placed on selecting culture conditions that minimize the use of substances of animal origin. Established methods, such as immunofluorescence staining, gene expression analyses, and live imaging, are used for comprehensive quality control and characterization of the 3D models. Morphological and metabolic evaluation methods are used to identify toxicologically relevant effects of test chemicals.

In addition to classical organoids, complex multicellular organoids (assembloids) and organ-on-a-chip models are being established. Furthermore, various organoid models will be interconnected to simulate the interactions of substances between organs in a multi-organoid system.