Drug development is a laborious and highly expensive process, averaging about 10-15 years and $1.3 billion for each new drug.¹ Despite the risky investment, the FDA estimates that more than 90% of drugs fail in human clinical trials after passing animal trials. Additionally, more than 100 million animals are tested each year.²
What if I told you we could test drugs without animals?
In 2010, researchers Dan Huh and Shuichi Takayama successfully created the Organ-on-Chips (OoC) technology, starting with the Lung-Chip. By 2014, the technology had been commercialized by the company, Emulate, leading to the development of over 15 different types of chips, modelling the kidney, skin, intestines and even the blood-brain barrier.³
OoC technology combines microfluidics – fluid flow through micro-channels – with cell cultures to replicate the functions of the real organ. While the basic structure remains the same, the epithelial cells are replaced to match the organ being modelled.⁴
Current research focuses on connecting multiple chips in order to replicate the complexity of the human body accurately. This aims to provide more reliable results during drug development and clinical trials.³
Other recent advances include the development of organoids and the transplantation of lab-grown cells. Organoids are three-dimensional miniature models of organs produced in vitro from stem cells, mimicking key functions and structures.⁵
With a shortage of donor organs, it is important to "look at ways of repairing damaged organs, or even provide alternatives to organ transplantation," says Dr Fotios Sampaziotis from the Cambridge Stem Cell Institute.⁶ Scientists from NIHR Cambridge Biomedical Research Center repaired a human liver using a 'perfusion system' and bile duct organoids. By injecting the organoids, they successfully repaired the damaged bile ducts and restored function.⁷
Professor Ludovic Vallier, joint senior author of this study, said: "This is the first time that we've been able to show that a human liver can be enhanced or repaired using cells grown in the lab," while noting that "further work" is needed.⁶
In 2022, the first ever lab-grown red blood cells were transfused to another person as part of the RESTORE trials. Professor Ashley Toye explains that the aim of these trials is to see if "red blood cells growing from stem cells in the lab are similar or better than a donor's own blood cells that they produced inside bodies". He further explains that if this works, it'll be a "world first" in allogeneic transfusions. While Professor Cedric Ghevaert added that if the trials are successful, the trials could reduce the need for frequent transfusions, transforming patient care.⁸
So, what does this mean for the future of medicine and drug development?
Dr. Paola Arlotta's lab is growing brain organoids for extended periods of time, allowing them to reach greater maturity and complexity. This allows them to effectively study how these organoids react to stimuli and model disease to understand the effect on different organs. Others, for example Dr. Carla Kim, are investigating the mechanism behind stem cell defects and how this leads to diseases by studying lung organoids.⁵
The impact of OoC technology, organoids and transplantation of lab grown cells is substantial. These advancements help model complex diseases such as cancer and neurodegenerative diseases and reduce animal testing significantly. OoC technology is extremely cost-effective and provides more reliable results as it models human physiology rather than that of other organisms, e.g. mice.
In personalised medicine, organoids or OoCs can be created from patient cells, reflecting the patient's unique physiology. This allows for tailored treatments to them and predictions of drug response. Additionally, these technologies offer new treatments where tissue damage is involved, through developments in regenerative medicine.
References
1. Derep, M. (2022) 'What's the average time to bring a drug to market in 2022' N-side. Available at: https://lifesciences.n-side.com/blog/what-is-the-average-time-to-bring-a-drug-to-market-in-2022
2. Akhtar A. (2015). 'The flaws and human harms of animal experimentation'. Cambridge Quarterly of healthcare ethics: CQ: the international journal of healthcare ethics committees, 24(4), 407–419. https://doi.org/10.1017/S0963180115000079
3. No name (April 27 2023) 'What are Organ Chips?' Emulate. Available at: https://emulatebio.com/an-introduction-to-organ-on-a-chip-technology/
4. Ingber, D. E. (2022) 'Human organs-on-chips for disease modelling, drug development and personalized medicine.' Nat. Rev. Genet. doi:10.1038/s41576- 022-00466-9.
5. No name (November 7 2017) 'Organoids: A new window into disease, development and discovery' Harvard Stem Cell Institute. Available at: https://hsci.harvard.edu/organoids
6.'Human liver repaired using cells grown in a laboratory for the first time' (2021) National Institute for Health and Care Research. Available at: https://www.nihr.ac.uk/news/human-liver-repaired-using-cells-grown-in-a-laboratory-for-the-first-time/27016
7. Sampaziotis, F. et al. 'Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.' Science (New York, N.Y.), 371(6531), 839-846. https://doi.org/10.1126/science.aaz6964
8. 'First ever clinical trial of laboratory grown red blood cells being transfused into another person' NHS Blood and Transplant. Available at: https://www.nhsbt.nhs.uk/news/first-ever-clinical-trial-of-laboratory-grown-red-blood-cells-being-transfused-into-another-person/
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