Tag Archives: organs-on-a-chip

The organs-on-chips market

After looking at the animal model market, I wondered about industry predictions for new developments in biomedical research that are human-relevant. Perhaps the field known as organs-on-chips holds the greatest promise for physiologically relevant, precisely controlled, and scalable engineered systems for use in the drug development process.

According to the Wyss Institute for Biologically Inspired Engineering at Harvard University, human organs-on-chips are microchips lined by living human cells that can be used in drug development, disease modelling and personalised medicine.

This is what they look like:

The development and testing of new drugs takes many years and is expensive. Very expensive. The cost of developing a new prescription drug is now around $2.6 billion. Traditionally, animals such as mice and dogs have been used in the development of  drugs. But around 90% of new drugs that have been found to be safe and effective in animals fail in clinical trials with humans.

To understand this high attrition rate between drug development and approvals, it is imperative to consider the drawbacks of the current methods of preclinical testing. Traditional 2D cellculture models can be effective in providing a broad indication of
compound efficacy and toxicity; however, they fail to represent cell function and physiology accurately because these cultures are monolayers as opposed to the 3D structures found in an intact organ and hence important tissue–tissue interactions are absent. Furthermore, upon the ingestion of a drug, it undergoes important transformations that allow it to be absorbed, distributed, metabolized and excreted (ADME). Examining these processes provides important information on the pharmacokinetics (PK) of the drug including dose, concentration and toxicity profiles. These parameters are traditionally tested in animals such as rodents and dogs along with a determination of safety and efficacy. However, a simple extrapolation of the PK and toxicity profiles from animals to humans is inaccurate owing to the vast differences in the genomes between the two species, as in the case of TGN1412. The development of assays that can better predict the safety, pharmacology and toxicity of a drug in humans is of paramount importance. Organs-on-chips is one such system that has the potential to reduce the dependence on animal testing and provide a more accurate readout of the safety and efficacy profile of a drug compared with conventional methods.
Source: Balijepalli, A., & Sivaramakrishan, V. (2017). Organs-on-chips: research and commercial perspectives. Drug Discovery Today, 22(2), 397-403.

In 2010, Donald Ingber at the Wyss Institute developed the first organ-on-a-chip, a lung-on-a-chip. Since then, academic institutions and private companies – sometimes working in partnership – have added miniature models of, for example, the liver, kidney, heart, bone marrow, cornea, brain, spleen and the human gut.

A multidisciplinary team at the Wyss Institute have also developed a chip that smokes cigarettes like a human. So there is no excuse to force mice to inhale cigarette smoke, as researchers at the Hunter Medical Research Institute and The University of Newcastle have done.

An organ-on-a-chip is about the size of a human thumb and “made from a flexible, translucent polymer. Microfluidic tubes, each less than a millimeter in diameter and lined with human cells taken from the organ of interest, run in complex patterns within the chip. When nutrients, blood and test-compounds such as experimental drugs are pumped through the tubes, the cells replicate some of the key functions of a living organ“.

Organs-on-chips can be used to study many biomedical phenomena. Apart from drug development and toxicity testing, other possible uses include, for example, personalised medicine (where stems cells derived from individual patients could be used to identify which therapies might be likely to succeed) or testing responses to biological and chemical  weapons.

As an alternative to conventional cell culture and animal models, human organs-on-chips could transform many areas of basic research and drug development. They could be applied to research on molecular mechanisms of organ development and disease, on organ-organ coupling and on the interactions of the body with stimuli such as drugs, environmental agents, consumer products and medical devices. Fundamental questions that might be addressed include how microenvironmental cues regulate cell differentiation, tissue development and disease progression; how tissues heal and regenerate (e.g., mechanisms of control of angiogenic sprouting and epithelial sheet migration); and how different types of immune cells and cytokines contribute to toxicity, inflammation, infection and multi-organ failure. When combined with patient-specific primary or iPS cells, or with gene editing technologies (e.g., CRISPR) to introduce disease-causing mutations, this technology could be used to develop personalized models of health and disease.
Source: Bhatia, S. N., & Ingber, D. E. (2014). Microfluidic organs-on-chips. Nature Biotechnology, 32(8), 760-772.

A recent article in the journal Drug Discovery Today provided the following examples of investment in organ-on-chip developments:

These are only a few examples of work on organs-on-chips. Worldwide, it is considered a multi-million, or even billion dollar market. For example, Yole Développement estimates that “the market could grow at a compound annual growth rate from 2017-2022 of 38-57% to reach $60M-$117M in 2022.” Another company, Accuracy Research, expects the organs-on-chips market to grow around 69.4% over the next decade to reach approximately $6.13 billion by 2025.

Large pharmaceutical and cosmetics companies are expected to start using organs-on-chips. Some companies have already partnerships with organs-on-chips developers, such as L’Oréal, Pfizer, AstraZeneca, Roche and Sanofi.

Ethical concerns are also at the heart of this new market: more than one hundred million animals are used in laboratory experiments worldwide every year, and could be replaced by pieces of microfluidic technology. Source: Yole Développement

Where does Australia sit in this market?

Some projects at the Australian Institute for Bioengineering and Nanotechnology, University of Queensland involve “the development of tumour-on-a-chip, organs-on-a-chip for rapid preclinical evaluation of potential nanomaterials for targeted therapeutics”. At the International Conference on Biomedical Engineering in December 2016, Professor Justin Cooper-White from this institute presented a keynote address on “Human kidney organogenesis from pluripotent stem cells on a chip”. There were other presentation on organs-on-chips, but none from Australia.

Two PhD Scholarships Bioengineering 3D in vitro model systems were recently advertised by Swinburne University of Technology.

A few academics with affiliations to Australian universities have published articles on organs-on-chips. However, it is unclear whether they are involved in the development of this technology. I could locate three articles in peer-reviewed journals on the topic:

  1. Nauman Khalid, a Postdoctoral Research Fellow at Deakin University has co-authored two articles, titled “Recent lab-on-chip developments for novel drug discovery” and “Industrial lab-on-a-chip: design, applications and scale-up for drug discovery and delivery“. I could not locate any information on the Deakin University website that links him to current work on organs-on-chips.
  2. One of the 14 authors of “Screening out irrelevant cell-based models of disease” lists Queensland University of Technology as an affiliation. In the article, the authors discuss new opportunities for exploiting the latest advances in cell-based assay technologies, of which organs-on-chips are one.
  3. Researchers from RMIT had a review of “Successes and future outlook for microfluidics-based cardiovascular drug discovery” published.

 

Where is the investment in organs-on-chips?

The published outcomes of the 2016 NHMRC Grant Application Round include two projects that involve work on organs-on-chips. The project descriptions are as follows:

Neurodegenerative diseases such as dementia and motor neuron disease are a major health burden for Australia and new approaches to treatment are urgently required. Essential trace elements such as copper, zinc and iron show major changes in neurodegneration, however, we do not understand how this drives disease processes. This proposal will develop an innovative 3D ‘brain on a chip’ cell model to probe the role of trace elements in brain pathology and identify exciting new treatments options.

and

New human cell culture models of Alzheimer’s disease are urgently needed to help translate drugs into successful patient outcomes. In this proposal we will develop an Alzheimer’s disease brain-on-a-chip that contains the major human brain cell types and neuropathological features of the Alzheimer’s. We will demonstrate the applicability of the model for identifying new Alzheimer’s disease drugs and diagnostics and show that the model can be readily adopted by Australian Alzheimer’s researchers.

Total grant funding for all 1,056 funded projects adds up to $828 million. The extent of the funding for the two organs-on-chips projects is not obvious from the published data, nor at which university, research institute or hospital the work will be undertaken.

I could not find information about investment on this technology by private companies.

body-on-a-chip Khalid et al 2017

Body-on-a-chip. Source: Khalid, Kobayashi & Nakajima, 2017.

Perhaps there is more work on organs-on-chips occurring in Australia, but I couldn’t find relevant information (I searched Google and PubMed). By and large, in Australia researchers continue to use archaic methods that hurt animals, are costly and ineffective. Despite the development of more human-relevant methods, the use of animals for research and education purposes is not decreasing in Australia.

The latest available statistics have just been published by Humane Research Australia. They “show that approximately 10.27 million animals were used in research and teaching in Australia in 2015, although this high number is largely due to NSW counting 4,123,049 native animals in environmental studies which involved observation only.” This compares to approximately 7 million animals in 2014.

Here we have a potentially multi-billion dollar market, and Australia is fiddling at the edges.

 

 

Non-animal research methods in the media

Over the last weeks articles about the development of research methods with the potential to replace animal models have caught my eye: One about bio-engineered muscles and two that report on new developments of organs-on-chips.

Tattooed man with a child. Source: Wikimedia/Jason Regan

Tattooed man with a child. Source: Wikimedia/Jason Regan

Bio-engineered muscles

Researchers at Duke University have created lab-grown human skeletal muscles that contract in response to electrical and other stimuli. They say the tissue works like regular muscles, but in a dish.

This model could be used in testing drugs for muscle diseases such as different muscular dystrophies, genetic metabolic diseases … and even diseases such as diabetes.

It could also be used to take cells from a patient, create functioning muscles in the lab and test various drugs to determine which drug and what drug dose would work best for that individual. It’s a new method that does not rely on animal testing.

Tissue chips

Researchers at the University of Wisconsin-Madison who work with tissue chips say these could replace animal studies. This project is funded by the U.S. National Institutes of Health and is part of the Tissue Chip for Drug Screening program. The UW-Madison researchers focus on brain cells.

Tissue chips are

clusters of interacting cells that mimic specific organs, such as a model of a developing brain. Using stem cells, miniature scaffolds and sophisticated computer programs, they’re crafting prototypes that could someday replace animal testing for drugs and serve as screening tools for environmental toxins.

With neural stem cells and hydrogels the researchers formed multilayered structures similar to the early human brain. With these tissue chips they tested 35 known toxins, such as arsenic and benzene, and 26 non-toxins, including arabinose and lactose. They found their system to be 93 percent accurate in predicting toxicity. This is much better than animal models, as nine out of ten new drugs that are safe and effective in animals fail in humans.

Mini synthetic organism instead of test animals

Researchers at the German Fraunhofer Institute have developed a multi-organ chip that replicates complex metabolic processes in the human body. The new chip can be used to test the active ingredients in new medications and cosmetics.

More on organs-on-a chip in these three video clips (though they’re not new):