Keeping the promise of organoids

Professor of Developmental Mechanics in the Department of Genetics at the University of Cambridge, Alfonso Martinez Arias shares his expert perspective on organoids in the field of developmental biology

A few years ago, a title and a photo captured the imagination of the world: Scientists managed to grow a miniature version of a human brain on a plate in the laboratory. Naturally, such a feat unleashed the imagination and hope of people, especially those with the disease. Regardless of whether similar discoveries were made and reported with mice before, the adjective “human” still has an impact on everything science-related. Soon word was that this would revolutionize the study of Mental Health, pave the way for curing illnesses and, of course, there were the inevitable claims to cancer cure.

These “mini brains were part of a menagerie of counterfeit lab-grown human organs and tissues, including disembodied eyes, livers, intestines and pancreas that came to light with this discovery.” How was this possible? What does it mean? It is sometimes difficult to disentangle the hype and hope in scientific research, but in this area it must be done, as the potential gains are huge but only if they are built on solid foundations and not on false expectations. Right now, understanding mental health with mini brains is not on the agenda, but understanding something about how cells make the brain is. If you want to build great buildings, you need a good foundation.

What are organoids

Structures that would have been cultured in the laboratory are known as “organoids” because they are imperfect replicas of real organs. They are the result of remarkable and still poorly understood capacities of special cells, stem cells. Cells do not live forever and most of the tissues in our body require constant renewal. This is what stem cells do. They manage to maintain themselves while providing a constant flow of material to repair damage and keep organs functioning.

For example, every day your body produces 200 trillion red blood cells to keep you in shape and stem cells in your gut 30 billion cells to take care of your digestion; it is the impressive power of these cells. The ultimate stem cells are embryonic stem cells (ESCs), derived from very young embryos, they can be grown almost indefinitely in culture, and at any time any of them can generate an entire organism.

Organoids are the result of the potential of stem cells. It’s not yet possible to grow blood in the lab, but intestinal and embryonic stem cells pave the way for much of what we may do in the future. A single intestinal stem cell can produce a coarse copy of the adult gut, an intestinal organoid, in vitro and directing ESCs in defined environments with specific chemicals, can produce rudimentary kidneys and lungs. It was these ESCs that were used to build mini brains. However, for now, we cannot control these processes, just watch them unfold.

The promise

It’s the beginning. Organoids are, in most cases, too imperfect to be useful, but the goal is to use these cellular devices to understand disease, test drugs, and even one day create substitutes for certain tissues and organs.

One of the main problems in regenerative medicine, in which we can replace a damaged organ or tissue with a healthy organ, is the matching of tissues between a donor and a patient. Work with organoids promises to solve this problem with the use of induced pluripotent stem cells (iPSCs): ESCs generated by converting an individual’s adult cells to ESCs which, in principle, can then be transformed into any what tissue and organ.

Thus, iPSCs make it possible to generate tissue matches for the patient because the donor is genetically the same. There is no doubt that it will happen in the future, but it will not happen any faster due to unfounded claims that it can happen, and we should avoid listening to the siren songs that are so common in this domain.

One of the obstacles to progress is “reproducibility”. In biology, when something works, it is able to make many good copies of itself; here are embryos that build organisms. Unfortunately, most organoids are now low frequency, heterogeneous, and non-functional. To break this deadlock, we need more basic research. Two areas will have an ongoing impact: developmental biology – which teaches us how animals develop – and engineering – which tells us how to control processes and make them efficient.

The path of promise

For now, however, as we realize the promise of iPSCs, gut organoids, possibly the most advanced and reproducible in the field of human organoids, provide a benchmark for some of the work that can be done. In a recent landmark study, scientists made intestinal organoids from cancer patients who were undergoing treatment and observed that the in vitro avatars responded to treatment as individuals did (http://science.sciencemag.org/content/359/6378/920.full). This opens up huge possibilities for using these organoids to rapidly test drugs and treatments showing the potential that lies ahead.

The emerging field of organoids at the intersection of stem cells, developmental biology and engineering will transform our understanding of how cells build organs and tissues, and in doing so, will pave the way for important applications in science. biomedical research. For this to realize its potential, we must resist the allure of statements that promise a lot in the short term present and invest in solid knowledge for the long term future.

Alfonso Martinez Arias

Professor of developmental mechanics

Department of Genetics, University of Cambridge, UK

Phone: +44 (0) 1223 766 742

ama11@hermes.cam.ac.uk

@AMartinezArias

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