The enormous complexity of the human brain makes it highly challenging to study, and physiological differences between humans and other mammals limit what we can learn from non-human models, particularly for neurological diseases. Researchers at the Vienna BioCenter made a major discovery that has the potential to overcome these limitations.

In 2013, Jürgen Knoblich and his team at IMBA published a landmark paper describing a method for in vitro cultivation of 3D brain-like structures, so called cerebral organoids (Lancaster et al., Nature 2013). Starting with pluripotent human stem cells, and using only a 3D support matrix and a spinning bioreactor to promote nutrient distribution, the researchers were able to obtain small organoids within a few weeks. These organoids contained several different types of nerve cells and their anatomical features closely resembled those of mammalian brains, demonstrating a remarkable self-organizing capacity. Cerebral organoids mimic early human brain development in a surprisingly precise way. This opens the door to neurodevelopmental studies and targeted analyses of human neurological disorders that are otherwise not possible. Using this technology, researchers at the Vienna BioCenter and around the world have already gained substantial new insights into how the human brain is formed, and into the defects that cause epilepsy, autism, and microcephaly (a neurodevelopmental disorder resulting in small brain size). Importantly, cerebral organoids have been very useful for research on the Zika virus, which is linked to microcephaly.

Since induced pluripotent stem cells can be used as the initial source of stem cells, organoids can be derived from patients’ blood or skin cells. Furthermore, the stem cells can be modified using genome-editing tools such as CRISPR/Cas9. Therefore, both natural and introduced mutations can be studied for their effects on organoid development and function. Excitingly, the Knoblich group has recently succeeded in creating cancerous organoids by introducing oncogenic mutations, providing a valuable model to study brain tumors (Bian et al., Nature Methods 2018). ‘Personalized medicine’ approaches may also be possible by producing many organoids from the same patient and screening them for the most effective drugs. The technology will help to bridge the translational gap between animal models and human clinical trials, allowing for more targeted clinical studies to reduce costs and boost success. A further important benefit is the potential to limit the numbers of animals needed for neurobiology research. Finally, the development of brain organoids from other mammalian species can reveal evolutionary aspects of neurogenesis. 

Understandably, scientists, patients, and the wider public have high hopes for the emerging field of organoid research, as the potential for basic research and modern medicine is huge. In 2017, together with Hans Clevers and Annelien Breedenoord, Jürgen Knoblich published a discussion of the ethical implications of human organoid research in “Science”, arguing for critical and responsible engagement with the new technology and providing a solid foundation for the establishment of framework conditions to achieve this.


Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA. Cerebral organoids model human brain development and microcephaly. Nature 2013; 501:373–9. 

Bian S, Repic M, Guo Z, Kavirayani A, Burkard T, Bagley JA, Krauditsch C, Knoblich JA. Genetically engineered cerebral organoids model brain tumor formation. Nature Methods 2018; 15:631–9