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ePaper created 2017-03-14, 10:25:37 | version 1.49.03
HEALTH 1 MICROPHYSIOLOGICAL ORGAN-ON-A-CHIP SYSTEMS AS ALTERNATIVES TO ANIMAL EXPERIMENTS J ulia Ro ga l, Chr is to p h e r P ro b s t , Sil v ia Ko lbus - H e r nan d ez , P e te r L o sk ill Restrictions on drug testing Drug development is an extremely expensive and time- intensive process. The major reason for the ineficiency of this process is the preclinical drug development requiring large animals or cell lines. Animal models and cell lines do not only play a key role in pharmaceutical research. They are also used in the cosmetics and chemical industries, as well as in academic basic research. However, even highly developed animal models are not able to replicate the complex human body, particularly human disease. Moreover, they are ethically questionable. models. Science, industry and public authorities now univer- sally recognize the potential of these systems. Organ-on-a-chip systems combine the unique features of classical cell assays (human genetic background) and animal models (3D tissue and blood circulation). They make it pos- sible to reduce the need for animal experiments according to the 3R principle (Replace, Reduce, Reine). Furthermore, they improve the translatability of preclinical results to clinical phases and thus make the entire development process more cost-effective, safer and faster. Basic building blocks of an organ-on-a-chip Immortalized cell lines are often of non-human or cancerous In the Attract Group “Organ-on-a-chip”, different microphysi- tissue origin and are typically cultured in two-dimensional monocultures. The physiological relevance of these cultures compared to human tissue is thereby very limited. Therefore, in many cases, the results obtained from experiments with cell lines or animal experiments do not correctly predict a drug’s effect in humans. Human in vitro models instead of animal experiments and cell lines The discovery of human induced-pluripotent stem cells (hiPS cells) has given scientists the opportunity to overcome many limitations of classical animal models, which is leading to a paradigm shift in the development of personalized and disease-speciic model systems. Speciically, the principle of organ-on-a-chip systems has evolved over the past few years from a conceptual idea to a possible alternative for animal ological organ-on-a-chip systems, also known as microphysi- ological systems (MPS), are being developed that replicate the in vivo structure and functionality of the respective organs. The primary component of these systems is the microphysi- ological environment. For this purpose, technologies from the ields of microfabrication, materials science and microluidics are used to create structures that physiologically mimic in vivo conditions. The use of microluidics enables the work with physiologically relevant small quantities of liquids and allows for the transfer and removal of soluble factors such as nutri- ents, drugs or metabolites. The second important component is the integration of human tissue, which is done by the use of hiPS cells instead of cell lines. By targeted differentiation of hiPS cells, it is possible 6 4