By Mihalis Kritikos.
Organoids are artificially grown organs that mimic the properties of real organs, providing new possibilities for treating diseases, drug development, and personalised and regenerative medicine.
Organoids are small clusters of human cells, grown in a laboratory environment to form three-dimensional structures that mimic the functionalities of real organs such as the liver, heart, and lungs. Organoids are either generated from resident progenitors in adult organs; or derived from one or a few cells from a tissue, embryonic stem cells or induced pluripotent stem cells, which can self-organise in three-dimensional culture owing to their self-renewal and differentiation capacities. These cell clusters are often grown in specially fabricated micro-containers that help the cells to arrange themselves, much as they would in an organ inside the human body. They closely resemble in vivo human tissue and possess the genetic characteristics of the people from whom they are taken, and so respond to drugs as the corresponding organ of the person in question would. These organ-like structures, which can be stored in biobanks, are not just a powerful tool to promote better understanding of the fundamental processes governing organ development in the human body, but also promise direct benefits for patient treatment and drug development.
Potential impacts and developments
As one of the most accessible and physiologically relevant models for studying the dynamics of stem cells in a controlled environment, organoids are expected to advance our understanding of tissue renewal, stem cell/niche functions and tissue responses to drugs, mutation or damage, as well as unlocking the mysteries of several brain diseases and neurological disorders. The blossoming of a technology that allows scientists to grow matter resembling brains, as well as livers, kidneys, intestines, and many other body parts, is seen as an important avenue to reconstituting organ functions ex vivo. Other possibilities include providing a sound model for preclinical screenings, targeted and personalised therapies, regenerative medicine applications, drug discovery and environmental toxicology testing.
The progress in generating organoids has extended organoid applications from a basic research tool to a translational platform with a wide range of downstream functions and uses that animal testing cannot offer, and could even revolutionise the drug discovery process. For instance, mini-guts can serve as a personalised drug-testing tool for cystic fibrosis (CF), whilst researchers are beginning to use brain organoids as accurate models for the study of a wide range of diseases such as autism, schizophrenia, and epilepsy.
Furthermore, liver-based cell organoids could form a complement to current organ transplantation to restore liver function of patients with metabolic liver disease and to serve as a model for metastasis growth, and for testing tumour cell response to current and newly discovered drugs. Pancreas organoids derived from adult pancreas stem cells are one of the most promising technologies for cellular and regenerative therapy. These ‘intestinoids’ already permit novel drug testing for cystic fibrosis and bowel cancer. Recently, scientists set up the world’s first ‘living biobank‘ to store patients’ tumours, and used the tissue to identify the most promising drugs for each person’s disease, while other scientists are making progress in creating larger assemblies of nerve cells, moving towards creating brain-sized organoids. In the near future, organoids will begin to enter routine medical use, as a way to shed light on diseases caused during embryonic development, or potentially as transplants to replace human patients’ diseased or failing natural organs. Organoids are also used to study what goes wrong, such as in neurons derived directly from patients with Alzheimer’s disease.
Alongside the benefits organoids could provide in terms of helping researchers to understand how real organs develop, and what can go wrong with that process, the scaling-up of organoids into reproducible and user-friendly systems and commercial manufacturing entails safety and ethical risks, given that culture methods are still in their infancy. Personalised organoids may facilitate the deployment of personalised medical trials, which may in turn pose new risks, and affordability concerns.
Similar conflicts may arise when considering the type of tissue generated. The closer scientists come to making a human brain, the greater the ethical issues. The concepts of human integrity in this context could be placed under significant threat.
Anticipatory law making
Although many of these technologies are still relatively new and require further validation and characterisation, the fact that organoids derived today from living tissues cultivated from participants’ stem cells may be stored for a very long/virtually infinite period of time underlines the urgency to deal with these issues now. Privacy requirements; terms and conditions of inclusion of participants in research/clinical trial settings; storage and use of organoids; and dissemination of results including incidental findings, all require attention. Informed consent is a major issue regarding inclusion of participants and the collection of their stem cells from residual tissue. Organoid biobanking also requires the development of tailor-made informed consent procedures that address the challenges associated with the fact that organoids are actually living mini-organs that could be used for a wide range of purposes, as well as the lack of an EU-wide legal framework on biobanks.
The use of organoids may complement or even reduce animal testing and the involvement of humans in an experimental setting, which may in turn trigger the modification of the existing medicinal testing, clinical trial and chemicals’ authorisation framework.
Another central issue is the question about ownership and commodification of bodily material, as well as how true to life an in vitro model of human development needs to be in order to be both scientifically valuable and ethically acceptable. As interest in organoid technology grows, the commercial development of more standardised, validated organoid culture media will also be valuable in ensuring that the organoid system becomes accessible to a wide range of academic and clinical scientists, thereby helping to maximise its potential.
This post is part of a series based on the EPRS publication ‘Ten more technologies which could change our lives‘, which draws attention to ten specific technologies and promotes further reflection about other innovations, in a follow-up to the 2015 ground-breaking publication ‘Ten technologies which could change our lives – potential impacts and policy implications‘. The publications explore the promises and potential negative consequences of these new technologies, and the role that the European Parliament as co-legislator could, and should, play in shaping these developments. The publications feed into the work and priorities of the Science and Technology Options Assessment (STOA) Panel and parliamentary committees.
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