Lifelike systems

Organ-on-chip and tissue-on-chip models continue to advance drug discovery

May 1, 2021
Ilene Schneider
Lifelike systems

Drugs developed using animal models like mice sometimes fail when taken to clinical trials because they do not accurately reflect human response. Human cell-derived organ and tissue models, therefore, are emerging as an added method of developing novel therapeutics.

Early 2021 brought news from several companies of new advances in organ-on-a-chip system and tissue-on-chip systems from the likes of CN Bio, Newcells Biotech, and the ENLIGHT project.

CN Bio, a developer of single- and multi-organ microphysiological systems, is developing single- and multi-organ COVID-19 models to investigate virology and immunology throughout the body, with a prolonged viable cell culture time for extended studies. The company has obtained a grant from Innovate UK, the United Kingdom’s innovation agency, to develop human-relevant microphysiological systems to advance investigations into SARS-CoV-2 infection. The funding will be used to develop and test advanced cell culture models representing different regions of the lung and linking these models to other organ systems to aid in developing therapeutics. 

“[Innovate UK’s] funding will enable us to develop and evaluate humanized single- and multi-organ lung models, with the aim of deploying these to researchers investigating COVID-19 infection and immunology, and ultimately strengthen the fight against the spread of the virus.,” says Dr. Tomasz Kostrzewski of CN Bio. CREDIT: CN Bio

The new 3D model creates an organotypic air-liquid interface improving upon the current organoid approach where cilia in the structure make it difficult to study viral infection. Information garnered from the new organ model will support researchers worldwide to better understand the infection and develop more accurate and efficient medicines that will hopefully have greater success in clinical trials. 

CN Bio’s technology is licensed from Massachusetts Institute of Technology (MIT) and Vanderbilt University, and has been successfully adopted by numerous pharma and academic partners.

According to Tomasz Kostrzewski, director of biology at CN Bio, “Through Innovate UK’s recognition of our technology’s potential, CN Bio is proud to be working on an additional COVID-19 project, to support the global effort in tackling the pandemic. This funding will enable us to develop and evaluate humanized single- and multi-organ lung models, with the aim of deploying these to researchers investigating COVID-19 infection and immunology, and ultimately strengthen the fight against the spread of the virus.”    

Meanwhile, Newcells Biotech— also based in the United Kingdom—which specializes in human stem cell models, has secured £5.25 million in funding from two existing backers, which will help Newcells to expand its growth in 3D tissue modeling for drug discovery. It will capitalize the biotech company’s international expansion in the United States adding to its existing commercial operations and launching new products. 

The commercial-stage life-science company is using its proprietary technology in stem cells and cell biology to build models of human tissues. The modeling technology is designed to improve the ability to generate data on the safety, efficacy, and pharmacology of drugs before human trials. The funding will accelerate the development of models for liver and lung conditions, which could advance the research into SARS-CoV-2 and its treatments, as well as fast-track the commercialization and launch of kidney and retina treatment models in North America.

“Over the last two years Newcells has made great progress in bringing innovative products and services to market that have delivered value to our global pharmaceutical customers,” said Newcells CEO Dr. Mike Nicholds. “Whether it be in understanding how new drugs interact with the kidney or the retina, our scientists have produced data that has helped lower the risk of early drug discovery projects ... Our vision is to bring the best in-vitro biology to market, improving the productivity of drug discovery and development.”

Another European-based project, ENLIGHT, is focused on the development of a 3D living model of pancreatic tissue. In this project, researchers are joining forces to enable better testing of diabetes medication. This model is being made with a new method of bioprinting invented at the UMC Utrecht and EPFL, along with specialized stem cells studied by ETH Zurich and the University of Naples. Eight European partners will create a new bioprinter that uses visible light to print stem cells three-dimensionally into functional pancreatic tissues. 

ENLIGHT’s project has obtained a four-year grant of €3.6 million from the European Innovation Council Fund Horizon 2020 to realize the first working tissue model within three years. Led by the UMC Utrecht, the multidisciplinary consortium consists of Ecole Polytechnique Federale de Lausanne, ETH Zürich, and Readily 3D (Switzerland); the University of Naples Federico II and Fondazione Giannino Bassetti (Italy); AstraZeneca (Sweden); and Rousselot (Belgium).

Rousselot’s biomedical team will develop an ultra-fast, visible light-induced, cross-linkable extracellular matrix (ECM) like hydrogel mimicking the pancreas structure using X-Pure. X-Pure biomedical grade gelatins are designed for 3D bioprinting and tissue engineering. 

Jos Olijve, scientific support manager and project contact from Rousselot, commented, “The topo- and geometrical cues and composition provided by the ECM together with morphogens and biochemical signals are important determinants of cell fate in vitro and in vivo. In other words, the design and purity of the ECM like structure is a crucial part of the ENLIGHT project.” 

These “personalized” models could accelerate drug discovery for pharmaceutical industries and reduce the burden on individual patients. The model could also be used for other diseases, such as cancer.

“With cells from a patient, practitioners can recreate the diseased tissue. Subsequently, a laboratory test can be performed to determine which candidate medication has the greatest effect. This spares patients a long search with unpleasant side effects, saves on treatment costs and leads to the best available care for individual patients,” explained Riccardo Levato, biofabrication researcher at the UMC Utrecht and coordinator of ENLIGHT.


Reference

CN Bio https://cn-bio.com/

Newcells Biotech https://newcellsbiotech.co.uk/

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