Month: October 2021

For academic researchers, keeping up with innovative approaches to solving problems can be a never-ending exercise as new technologies displace older methods of experimentation. At Queen Mary University London (QMUL), scientists across many disciplines are using in vitro models to explore the fundamental biology of health and disease and to develop and test novel therapeutic approaches, such as pharmaceuticals, regenerative medicine techniques, medical devices, and biomaterials. QMUL’s Centre for Predictive in vitro Models (CPM) opened in 2019, providing multidisciplinary research focusing on the development and use of predictive in vitro models. This covers a wide range of model systems including 2D and 3D cell culture models, organoids, microphysiological systems, organ-on-a-chip technology, and other types of in vitro models.The vision of the CPM is to facilitate the implementation of innovative in vitro models in orderto deliver the highest quality discovery science and transformative healthcare solutions. Within the CPM, the University has established the Queen Mary+Emulate Organs-on-Chips Centre. This provides access to Emulate’s platform technology and associated 2D (2 Dimensional) and 3D cell culture models for staff at QMUL and across the wider UK Organ-on-a-Chip Technology Network. 

Organs-on-Chips can predict human response with greater precision and control than cell culture or animal-based testing. As such, they are used to test therapeutics and better understand how the body works. For scientists who want to move from static culture models to dynamic organ-chip technology, the QM+Emulate Organs-on-Chips Centre provides access to and support for Emulate Organ-chips. With a project in mind, researchers can perform experiments using Emulate’s established Organ-Chip models, including Brain, Liver, Proximal Tubule Kidney, and Intestine, or they can develop models of their own design using Emulate’s Basic Research Kit. Emulate’s technology can be configured to recreate a wide range of different organ tissues and disease models. They recreate the body’s dynamic cellular microenvironment, including tissue interfaces, blood flow, immune cell interactions, and mechanical forces. Staff at the Centre provide expert-level training on the platform and assistance with experimental design for proof-of-concept studies.

Much of the work being done at the QM+Emulate Centre using Organ-Chips is breaking new ground for in vitro modeling and providing unprecedented biological insight. In many experimental situations, two-dimensional cell culture methods are unable to replicate the appropriate cellular microenvironment, and animal models are unsuitable due to species differences. One example of current Organ-Chip research at Queen Mary involves the developed breast cancer bone metastasis model. This provides a model of mechanically active bone tissue that enabled analysis of cancer cell migration, proliferation, and invasion.

This research, funded by Cancer Research UK, the Engineering & Physical Sciences Research Council (EPSRC), and the EU, is being led by Prof. Martin Knight’s group based in the Bioengineering department within the School of Engineering and Materials Science. The group recently published a paper which sought to understand if the osteocyte environment, which includes mechanical stimulation via fluid shear stress, can regulate the behavior of breast and prostate cancer cells. The research conducted by Dr. Stefaan Verbruggen discovered that osteocytes signaled for decreased proliferation of cancer cells, but mechanical loading reversed this phenomenon in breast cancer cells. With the help of the microfluidic Organ-Chip model, the authors demonstrated the importance of replicating the mechanical tumor environment, which led to increased invasion potential of cancer cells. Understanding this mechanism will help the research team develop new treatments for breast and prostate cancer bone metastasis, which currently have very poor survival rates. 

Research successes, like modeling bone metastasis, are generating great interest in in vitro predictive model systems in the UK. “We are establishing proof-of-concept programs to enable researchers to get started with Organ-Chip models and are currently supporting more than 20 groups building new models including tendon, bone, cartilage, placenta, and synovium in addition to developing new protocols for Emulate’s existing models,” said Dr. Clare Thompson, Emulate Centre Scientist. “Many are really drawn to the imaging capabilities of the chip models. In addition to viewing fixed chips with confocal microscopy, you can perform live imaging studies to look at how your cells are behaving in real time- this is always quite exciting for our researchers.” 

Since its opening, the QM+Emulate Organs-on-Chips Centre has supported a variety of grant applications for researchers at Queen Mary University and other institutions. Research topics range from testing new cancer therapeutics to modeling immune cell interactions to asking basic questions in biology and physiology that examine how mechanical forces impact organs and cells. The Centre also provides opportunities for collaboration with Emulate as well as support for commercialization and translational impact.

For more information on getting started with Organ-Chips at QMUL, visit https://www.cpm.qmul.ac.uk/  

In April 2021, a bipartisan congressional committee took a big step towards modernizing the way therapeutics are developed in the United States by proposing the FDA Modernization Act of 2021—an amendment to the 1938 Federal Food Drug and Cosmetics Act (FFDCA). Among other stipulations, the FFDCA currently mandates the use of animal testing during preclinical drug development. The FDA Modernization Act of 2021 aims to change this by broadening the scope of acceptable preclinical models for drug development, enabling researchers to test a drug’s safety and efficacy using more advanced and humane methods in place of animal testing wherever possible. Such an amendment, if enacted, could pave the way for faster, more effective, and more humane therapeutic development.

Emulate is proud to endorse the FDA Modernization Act of 2021. Here’s why: 

In its current state, the FFDCA stipulates that drugs can only advance to clinical trials if there is enough data describing the drug’s chemistry, manufacturing, and “primary data tabulations from animal or human studies.” The goal of this stipulation is to ensure that drugs are well characterized from both a chemical and biological perspective before they can be used for clinical trials.

When the FFDCA was enacted in 1938, animal models seemed like the best way for drug developers to study how therapeutics might act within a biological setting. In theory, then, animal testing should ensure that only the safest, most effective drugs make it to clinical trials. However, over the years, evidence has accumulated suggesting that this isn’t always true and that better models are needed.

Some studies estimate that as much as 89% of novel drugs entering clinical trials ultimately fail, with as much as 50% of those failing due to toxicities unanticipated by animal models.  

Take, for instance, the dismal failure rate among cancer therapeutics that initially show promise in animal trials, but only about 8% of which successfully progress through clinical trials. Some studies estimate that as much as 89% of novel drugs entering clinical trials ultimately fail, with as much as 50% of those failing due to toxicities unanticipated by animal models.  

The FDA Modernization Act of 2021 opens the door for researchers to use the best models available to them. With the ability to use better model systems — like Organs-on-Chips — it is likely that candidate drug success rates will increase.

Industry reports estimate that it takes 10 to 15 years for a drug to go from initial hit discovery to clearing clinical trials. Any step we can take to shorten this timeframe without sacrificing drug quality is paramount.  

One area for improvement is in preclinical testing. Typically, drug development begins with a large library of potential candidate therapeutics. Initial screening identifies candidates that are most likely to succeed, and these progress through iterative cycles of adjusting the chemical structure and screening for improved properties. Eventually, multiple candidates are ready to progress into more complex systems to analyze efficacy and safety in a biological setting.  

Today, this often means using animal studies. Replacing animal studies with more advanced, human-relevant models has significant potential to improve decision-making throughout the drug discovery and development lifecycle as well as decrease the number of adverse effects that occur in clinical trials.  

Additionally, working with animal models can be very resource intensive, as the animals require adequate housing, food, and care. In contrast, models like Organs-on-Chips are much more compact and require less oversight. Estimates suggest that, relative to in vitro models, animal testing is 1.5- to 30-times as expensive. Therefore, removing the need for animal testing is likely to significantly decrease the cost of drug development, which today can exceed $1 billion.

Finally, with the existence of advanced cell-based and microphysiological systems, the FFDCA’s stipulation that animal testing is necessary for preclinical safety and efficacy studies is outdated and inhumane. While animals have a profound and critical role in many aspects of scientific research, the using animals in place of more effective models is both counterproductive and needlessly cavalier about the animals’ welfare.   

The FDA Modernization Act of 2021, consistent with the FDA’s initiative to advance regulatory science, will promote animal welfare without compromising scientific research and will ensure that we are better prepared for future challenges and opportunities. At Emulate, we believe that using the most predictive technologies available will ultimately streamline drug development and spur innovation, benefiting both patients and the pharmaceutical industry.