Testing Drugs on Stem Cell Based Models / Replacement for Animal Testing

Human stem cells can be used in the field of developing new drugs and testing pharmacological substances in the form of in vitro cell models which map the influence of substances on cellular mechanisms. 

Substance screening / identifying new active substances

The efficacy of new drugs can be investigated using the ADMET criteria (absorption, distribution, metabolism, excretion, toxicity). Synthetic tissue models are particularly suitable for identifying and testing new active substances and therefore avoiding ethically controversial and often expensive animal testing. The properties of primary human cells and thus also human reactions to an active substance can only be mapped in a limited way using animal testing. A targeted investigation of active substances on special cell types, such as nerve or heart cells, can often only be carried out by using human pluripotent stem cells. The production process for testing systems obtained from stem cells is becoming increasingly automated and achieves a high degree of standardisation. Some of the models are produced with the aid of embryonic stem cells or induced pluripotent stem cells. 

Detection of undesirable side effects

This includes the teratogenicity (damage to embryo or foetus) of drugs, which can only be simulated in a limited way in animal testing. The drug thalidomide (Contergan) is an example of a teratogenic effect which could not be proven in animal testing as the metabolism of some mammals reacts differently than the human metabolism to the molecular dosage form of the drug. The lack of comparability between animal testing and clinical testing, on the one hand, and the high standards for approving a drug, on the other, have given rise to the demand for alternative testing methods. Cell models with human stem cells could prove an important approach. Along with a possible teratogenic effect, neurotoxic and cardiotoxic effects could be differentiated on the stem cells of each respective tissue. The interaction of various drugs via a common metabolic path in the liver could be investigated using liver stem cells. Also, by applying existing medicines or active substances to human stem cells it is possible to find a better fit for treatment. 

Löser, P. / Hanke, B. / Wobus, A. M. (2011): Humane pluripotente Stammzellen – Perspektiven ihrer Nutzung und die Forschungssituation in Deutschland. In: Naturwissenschaftliche Rundschau 64 (9), 453–465. Online Version (German)

Rosner, M. / Reithofer, M. / Fink, D. / Hengstschläger, M. (2021): Human embryo models and drug discovery. In: International Journal of Molecular Science 22 (2). DOI: 10.3390/ijms22020637. Online Version

Nuciforo S. / Heim M. H. (2021): Organoids to model liver disease. In: JHEP Reports 3 (1). DOI: 10.1016/j.jhepr.2020.100198. Online Version

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