Organ-on-a-Chip Platform

Our human, physiological cell culture systems are created in a specially developed biochip, made of biocompatible plastic, suitable for chemical and toxicological tests. By integrating a porous membrane into the biochip, we achieve a spatial separation of the blood vessel and organ-specific tissues. The properties of the membrane allow an exchange of nutrients and oxygen as well as important cell interactions between the tissues (e.g. paracrine signal molecules; transmigration). Cells can be individually introduced into the biochip and continuously supplied with nutrients and oxygen via channels and exposed to mechanical stimuli. This is of decisive importance for the tissue development and arrangement as well as the functional maintenance of the tissue over weeks. By integrating sensors to monitor oxygen consumption and barrier function, we are able to monitor tissue viability and functionality in real time. This enables us to detect the toxicity of active substances in a very sensitive and timely manner.

Applications

Our human organ models can be used in various fields:

Preclinical phase of drug development (prior to animal testing)

Review of novel therapy options (e.g. uptake, toxicity of nanoparticles)

Toxicity determination for newly developed chemicals

Cell-based culture systems in basic research

Food toxicology

Human disease and infection models for drug testing or the investigation of mechanistic questions

Models

Liver Sinusoid

The liver is the central metabolic organ in our body. It is responsible for the metabolism of plasma proteins, carbohydrates and lipids and for the degradation of a large number of drugs and toxins and is therefore of particular importance in the development of new drugs.

Our human liver sinusoid model is based on the anatomical basic unit of the liver, the liver sinusoid, in terms of structure, cell composition and culture conditions and can currently be functionally maintained over 10 days. Through the integration of immune cells, side effects/toxicity of active substances can be made visible at an early stage with this system.

Alveolus

The task of the lung is the exchange of gases, which is made possible by a large surface area created by the distal branching of the trachea into bronchi, bronchioli and alveoli. With our human alveolar model, human alveolar epithelial and endothelial cells as well as essential components of the immune system can be functionally cultivated for 21 days. Hereby toxicities of inhaled substances (e.g. respiratory sensitizers, allergens, fine dust / diesel) can be tested. The model is also suitable for conducting infection studies and testing new therapeutics.

Intestine

The intestine is a very important part of the digestive tract. It serves the absorption of nutrients, the regulation of the water balance, the formation of immune cells as well as the production of hormones and messenger substances.

Our three-dimensional intestinal model, which can be functionally maintained over 15 days, forms Villus-like structures containing the characteristic cell types as well as central tissue-resistant immune cells. This model can be used to investigate questions regarding the uptake of active substances and their transport into the bloodstream as well as direct toxic effects on the intestinal tissue and its barrier function.

By combining these three human organ models, we can also address and analyze a wide range of questions regarding ADMET (absorption, distribution, metabolism, excretion, toxicology) of an active substance.

Pipeline/model development

Human biochip-based organ models of the kidney and blood-brain barrier as well as disease models of the liver and lung are currently under development. Furthermore, these models can be interconnected in modules for more complex substance testing. The complexity of our models is freely scalable. Biological components can be expanded or reduced according to customer requirements. Individual problems can also be addressed by targeted manipulation of individual cell types. Last but not least, the system can also be specifically adapted to customer requirements, especially with regard to defined disease models.

Puplications

Microphysiological systems

2018

Pein H., Ville A., Pace S., Temml V., Garscha U., Raasch M., Alsabil K., Viault G., Dinh CH., Guilet D., Troisi F., Neukirch K., König S., Bilancia R., Waltenberger B., Stuppner H., Wallert M., Lorkowski S., Weinigel C., Rummler S., Birringer M., Roviezzo F., Sautebin L., Helesbeux JJ., Séraphin D., Mosig AS., Schuster D.,  Rossi A., Richomme P., Werz O., Koeberle A.; Endogenous metabolites of vitamin E limit inflammation by targeting 5‑lipoxygenase. Nature Communications, 2018, e-pub ahead

Raasch M, Fritsche E, Kurtz A, Bauer M, Mosig AS. Microphysiological systems meet hiPSC technology – New tools for disease modeling of liver infections in basic research and drug development, Adcanced Drug Delivery Reviews, DOI: 10.1016/j.addr.2018.06.008

2017

Gröger M, Dinger J, Kiehntopf M, Peters FT, Rauen U, Mosig AS Preservation of Cell Structure, Metabolism and Biotransformation Activity of Liver-on-chip Organ Models by Hypothermic Storage. Advanced Healthcare Materials, 2017, September 17, doi:10.1002./adhm.201700616

Fahrner R, Möller A, Press AT, Kortgen A, Kiehntopf MD, Rauchfuss F, Settmacher U, Mosig AS Short-term treatment with taurolidine is associated with liver injury. BMC Pharmacology and Toxicology, 2017, 18(1) doi: 10.1186/s40360-017-0168-z

Mosig AS, Nawroth J, Loskill P. Organs-on-a-chip: Neue Perspektiven in der Medikamentenentwicklung und Personalisierten Medizin. Deutsche Zeitschrift für Klinische Forschung, 1/2017

Gröger M, Lange M, Rennert K, Kaschowitz T, Plettenberg H, Hoffmann M, Mosig AS. Novel approach for the prediction of cell densities and viability in standardized translucent cell culture biochips with near infrared spectroscopy. Engineering in Life Sciences, 2017, doi:10.1002/elsc.201600162

2016

Mosig ASOrgan-on-chip models: new opportunities for biomedical research, Future Science OA, 2016, FSO130, doi: 10.4155/fsoa-2016-0038, Editorial

Gröger M, Rennert K, Giszas B, Weiß E, Dinger J, Funke H, Kiehntopf M, Peters FT, Lupp A, Bauer M, Claus RA, Huber O, Mosig AS. Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model. Scientific Reports, 2016, 6: 21868

Raasch M, Rennert K, Jahn T, Gärtner C, Schönfelder G, Huber O, Seiler AEM, Mosig AS. An integrative microfluidically supported in vitro model of an endothelial barrier combined with cortical spheroids simulates effects of neuroinflammation in neocortex development. Biomicrofluidics, 2016, 10(4): 44102 – 441016

2015

Rennert K, Steinborn S, Gröger M, Ungerböck B, Jank AM, Ehgartner J, Nietzsche S, Dinger J, Kiehntopf M, Funke H, Peters FT, Lupp A, Gärtner C, Mayr T, Bauer M, Huber O, Mosig AS. A microfluidically perfused three dimensional human liver model. Biomaterials, 2015, 71:119-31.

Raasch M, Rennert K, Jahn T, Peters S, Henkel T, Huber O, Schulz I, Becker H, Lorkowski S, Funke H, Mosig AS. Microfluidically supported biochip design for culture of endothelial cell layers with improved perfusion conditions. Biofabrication, 2014, 7(1):015013.

Disease and Infection models

2016

Rennert K, Otto P, Funke H, Huber O, Tomaso H, Mosig AS. A human macrophage – hepatocyte co-culture model for comparative studies of infection and replication of Francisella tularensis LVS strain and subspecies holarctica and mediasiatica. BMC Microbiology 2016,16(1):2

Immune cells

2017

Pergola C, Schubert K, Pace S, Ziereisen J, Nikels F, Scherer O, Hüttel S, Zahler S, Vollmar A, Weinigel C, Rummler S, Muller R, Raasch M, Mosig AS, Koeberle A, Werz O. Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy. Scientific Reports, 2017, 7:41434-41446

Rennert K, Nitschke M, Wallert M, Keune N, Raasch M., Lorkowski S, Mosig ASThermo-responsive cell culture carrier – effects on macrophage functionality and detachment efficiency. Journal auf Tissue Engineering, 2017 Aug 25, 8:2041731417726428

Thomas L, Rao Z, Gerstmeier J, Raasch M, Weinigel C, Rummler S, Menche D, Müller R, Pergola C, Mosig AS, Werz O. Selective upregulation of TNFα expression in classically-activated human monocyte-derived macrophages (M1) through pharmacological interference with V-ATPase. Biochemical Pharmacology, 2017, 130:71-82

2016

Rennert K, Heisig K, Groeger M, Wallert M, Funke H, Lorkowski S, Huber O, Mosig AS. Recruitment of CD16+ monocytes to endothelial cells in response to LPS-treatment and concomitant TNF release is regulated by CX3CR1 and interfered by soluble fractalkine. Cytokine, 2016, 83: 41–52

Gröger M, Rennert K, Giszas B, Weiß E, Dinger J, Funke H, Kiehntopf M, Peters FT, Lupp A, Bauer M, Claus RA, Huber O, Mosig AS. Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model. Scientific Reports, 2016, 6: 21868

2015

Maeß M, Keller AA, Rennert K, Mosig AS, Lorkowski S. Optimization of the transfection of human THP-1 macrophages by application of Nunc UpCell technology. Analytical Biochemistry, 2015, 479:40-42

2013 und früher

Wallert M, Mosig AS, Rennert K, Funke H, Ristow M, Pellegrino RM, Cruciani G, Galli F, Lorkowski S, Birringer M. Long-chain metabolites of α-tocopherol occur in human serum and inhibit macrophage foam cell formation in vitro, Free Radical Biology & Medicine, 2013, 68:43-51

Mosig AS, Rennert K, Krause S, Kzhyshkowska J, Neunubel K, Heller R, Funke H. Different functions of monocyte subsets in familial hypercholesterolemia: potential function of CD14+ CD16+ monocytes in detoxification of oxidized LDL. FASEB Journal, 2009, 23(3): 866-874

Mosig AS, Rennert K, Buttner P, Krause S, Lutjohann D, Soufi M, Heller R, Funke H. Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism. BMC Medical Genomics, 2008, 1: 60-72

New therapeutic options/ nanoparticle

2016

Englert C, Trützschler AK, Raasch M, Bus T, Borchers P, Mosig AS*, Träger A*, Schubert US*. Crossing the blood-brain barrier: Glutathione-conjugated poly(ethylene imine) for gene delivery.Journal of Controlled Release, 2016, 30 (241):1-14. (* shared senior authorship)

2015

Rinkenauer AC, Press AT, Raasch M, Pietsch C, Schweizer S, Schwörer S, Rudolph KL, Mosig AS, Bauer M, Traeger A, Schubert US. Comparison of the uptake of methacrylate-based nanoparticles in static and dynamic in vitro systems as well as in vivo. Journal of Controlled Release, 2015, 216:158-68