Organoids: from science fiction to reality

Imagine if we could predict whether a molecule would work safely and effectively against a disease by testing it with "mini-organs" – tiny, lab-grown versions of the organs in our body, e.g. livers, lungs. We would be able to fast-track promising drug candidates into the clinic and dramatically reduce the use of often unreliable animal models.

This might sound like science fiction from the mind of Mary Shelley, yet researchers have been developing this concept since the 1970’s. In recent years, advances in cell culture technology, combined with our expanding knowledge of how stem cells work, has led to the creation of “organoids” for advancing medical research.

Organoids are tiny, self-organised three-dimensional tissue cultures that are derived from stem cells. Such cultures can be crafted to replicate much of the architectural and functional complexity of a human organ, or to express selected aspects of it, like producing only certain types of cells.

Roche has been keenly involved in this field, exploring the use of organoids and “organ-on-a-chip” technology, to create in vitro models that could predict the activity of molecules with greater accuracy than current methods. An example is Roche’s Institute of Human Biology (IHB), focused on breaking new ground and driving development in the field of organoids.

Organoids grow from stem cells—cells that can divide nearly indefinitely and produce different types of cells as part of their progeny. Scientists have learned how to create the right environment for the stem cells so they can self-organise, forming tiny structures that resemble miniature organs composed of many cell types. To date, researchers have been able to produce organoids that resemble the brain, kidney, lung, intestine, stomach, and liver, and many more are on the way.

Organoids derived from patient cells represent useful tools for the study of disease mechanisms because they replicate the complexity of the in vivo disease phenotype while still retaining the accessibility of in vitro systems.

Biobanks of organoids are now being generated, for example from cancer patients, which could be used to identify drugs effective against a broad spectrum of disease phenotypes. In personalised healthcare applications, patient-specific organoids may help identify the best drug for individual patients. In regenerative medicine, organoids derived from healthy donor cells, or from patients after genetic correction, can be used as a source of cells or tissues.

One major advantage of organoid cultures for disease modelling, compared with traditional cell cultures of a single cell type, is their ability to mimic pathologies at the organ level. Added to that, some diseases are peculiar to humans and therefore not replicable in animal models. The idea that organoids can model human pathologies has opened the door to studies on the feasibility of drug testing and screening applications.

The path towards a broad-ranging translation of organoid technology into real-life preclinical and clinical applications remains challenging. However, much has already been achieved in revealing the amazing level of self-organisation that stem cells can display when cultured under the appropriate conditions, as well as in expanding the list of organoid types.

Overcoming these challenges at the IHB requires a concerted, multidisciplinary effort. Bringing together our deep expertise in human biology, engineering and data analytics will have a significant impact in the coming years, enabling science fiction to soon become a reality for the benefit of patients.

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Institute of Human Biology (IHB)

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