Saturday, 01 July 2023 09:32

Berlin: International Congress on Multiorgan-on-a-Chip with overwhelming contributions Featured

This year's World Summit on Microphysiological Systems was held in Berlin from June 26 to 30. 1,297 participants from numerous countries had registered. It was impressive to see how many young scientists dedicated themselves to the development of animal-free methods with the ultimate goal of finding better treatments through human-specific research, reducing the financial burden and time required to do so, and replacing animal experimentation.

Compared to the last MPS Summit in New Orleans, the number of participants had once again increased significantly. More than half of the participants were scientists - many young researchers presenting their current results, more than a third came from industry, but there were also numerous representatives from regulatory authorities, government and, of course, non-governmental organizations.


MPS Summit 2023 in Berlin.
Photo: Christiane Hohensee

The congress was preceded by a series of educational workshops in which start-ups presented their state-of-the-art developments to interested aspiring scientists.

With few exceptions, scientists presented results from developed miniaturized organ-like systems from humans and not from animals. Numerous research groups and manufacturers provided information about newly developed microfluidic systems, culture media without animal ingredients, biomarkers, imaging methods or computer solutions.

Only a small selection can be presented here.

Start-ups strongly present

Numerous start-ups enriched the congress with their service offerings. Often they were also present with lectures or posters about current research results. For example, the start-up DNTOX, a spin-off of the Leibniz Institute for Environmental Medicine Research Düsseldorf, or the already longer established companies TissUse GmbH from Berlin, Hesperos Inc. from Orlando, Florida, as well as emulate Inc. from Boston, Massachusetts, USA.

For example, DNTOX led by Prof. Ellen Fritsche und Dr. Katharina Koch has developed an in vitro test battery based on its own neurosphere assay using human neural progenitor cells (hNPCs). The goal is to cover the hormone-sensitive key events of nerve and brain development when testing chemicals for hormone efficacy. Using their battery of tests, the researchers identified both sex- and species-specific dependencies of hormonal activity during brain development.

The Japanese company USHIO Inc. used artificial intelligence to analyze neurite growth in the culture after it had been treated with chemicals. This allows more accurate conclusions to be drawn than with conventional imaging techniques.

Big topic: disease models on the chip

Malaria still affects 200 million people worldwide and kills 600,000 of them. That's why the Orlando-based human-on-a-chip company Hesperos led by Prof. James Hickman has developed a malaria disease model containing four human tissue constructs to research better treatments. The cell types used include hepatocytes, a white blood cell type from the spleen (splenocytes), endothelial cells and recirculating red blood cells, which are cultured in a microfluidic system. An infection with Plasmodium falciparum can be simulated. Chloroquine is a commonly used drug for the treatment and chemoprophylaxis of malaria.

In most cases, gingivitis is caused by bacteria in the oral cavity. The disease is very common among the population. Prof. Dr. Chiara Ghezzi and her team at the University of Massachusetts Lowell have developed a 3D anatomical model of human gum tissue with bacteria in the oral cavity to study the interaction of the microbiom. The tissue is based on human primary cultures, a natural oxygen gradient in the recreated gingival pocket could also be simulated. The model will be used for studies investigating host-pathogen imbalances in gingivitis and periodontal disease.

During inflammatory bowel disease, therapeutic probiotic bacteria can restore the homeostasis. Emulate Inc. has introduced a physiologically relevant human colon intestine model to study the intestinal epithelium. It was examined to what extent Lactobacillus rhamnosus is able to protect the intestinal epithelium from inflammation.  The treatment with interferon-gamma led to signs of damage to the colonic epithelium in a subproject. A common immunosuppressant used to cure ulcerative colitis, but also Lactobacillus rhamnosus, led to a protection of the intestinal epithelium and suppression of inflammation.

The Pisa-based company IVTech has developed a model that can simulate high blood pressure and cardiac arrhythmias in a microfluidic system. The technique is of great interest to researchers of vascular disorders such as artherosclerosis, among others, who could use such a model.

Hypertension model
Photo: Christiane Hohensee

The endometrium is a complex mucosal barrier that can proliferate in women at unusual sites, travel throughout the body, and lead to debilitating pain and infertility. The condition is called endometriosis. In a microphysiological model, British-American researchers led by Linda Griffiths, PhD, from the Massachusetts Institute of Technology (MIT) and others cultured an endometrium that was physiologically disturbed and exhibited tissue damage, as occurs in endometriosis.

A focus on development and reproduction

Simulating the human reproductive tract is not easy. Despite hormonal and functional differences between humans and rodents, countless animal experiments are still currently performed. Even in vitro models combine either for ethical reasons, e.g. mouse blastocytes implanting in human uterine tissue. Or is it simply still too difficult to replicate human spermatogenesis in vitro.

Using a new microfluidic platform, Prof. Angela Russo and Prof. Joanna E. Burdette of the College of Pharmacy at the University of Illinois, Chicago, studied the effects of high concentrations of the hormone testosterone on human fallopian tube epithelium. Androgens affect ovarian function by altering follicular development, growth and survival. Elevated androgen concentrations are also associated with an increased risk of ovarian cancer. In the study, elevated testosterone level led to an upregulation of the signaling protein WNT4, which is thought to play a cancer-promoting role in many cancers, and the migration and invasion of immortalized human fallopian tube cells.

Roser Vento-Tormo, PhD, of the Wellcome Sanger Institute in Cambridge, UK, and her team have created a comprehensive map of developing and adult human reproductive tissue. It is being used to study the development of reproductive diseases and therapies. But it can also serve as a basis to develop new in vitro tests. In doing so, the team used single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescence microscopy. In chromatin accessibility assays, the cell genome was disrupted by enzymatic or chemical methods, making the inaccessible regions accessible. The DNA could then be isolated and sequenced.

A British-Dutch research team involving Dr. Iris Müller from Unilever has unveiled new in vitro tests for developmental and reproductive toxicity endpoints (DART). This is needed because under the European Union's Green Deal, there are plans to increase testing of chemicals for their effects on reproductive organs, their impact on development, hormones and the immune system. The new animal-free methods presented here are a combination of several tests. These include a mathematical characterization and prediction of the reaction rates of substances in organs and tissues of an organism, as well as the measurement of the physiological stress load of cells and the mRNA expression of cells in high-throughput. In addition, a number of in vitro developmental and reproductive toxicity tests have been expanded to include the human stem cell-based in vitro assay ReproTracker® from Toxys and the in vitro assay devTox quickPredict™ from Steminas. A comparison of the results with literature studies showed more than 80 percent agreement. To refine the results to allow a safety decision relevant to humans, other microphysiological systems have been discussed such as placental transfer models to calculate fetal exposure.

A team of researchers at the University of Washington, Seattle, led by Prof. Elaine Faustman, has constructed an in vitro model to test for toxicity mechanisms of postnatal testicular development. Unfortunately, they used primary rat testicular cells for this purpose. The cells were grown in Matrigel on a micro-culture plate. At regular intervals, the culture medium was probed for testosterone and RNA was isolated from the cells for further study. The physiologically relevant testicular development in the model was confirmed and testosterone production was increased via follicle-stimulating hormone and luteinizing hormone. Phthalates, on the other hand, triggered inflammatory signals and impaired somatic cell development.

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