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Brain organoids, three-dimensional models of the brain, are a boon to neuroscience, making it possible to study the development, evolution and disease of the brain in a model that is based on human stem cells. Now, a consensus paper published in Nature by leading researchers in the brain organoid field, including Jürgen Knoblich at IMBA, outlines a framework for working with and further improving brain organoids.
Over a decade ago, Jürgen Knoblich and his team at IMBA kickstarted the study of brain organoids: In a landmark paper published in 2013, Knoblich and postdoc Madeline Lancaster presented the first brain organoids for studying human disease and development. Brain organoids harness stem cells’ inherent ability to self-organize: Given the right signals, stem cells derived from skin samples of patients and healthy donors can be induced to form models that mimic specific timepoints and areas of the brain, such as early embryonic development or cortical neurons.
As brain organoids replicate aspects of the brain’s physiology, organoids hold the potential to reveal new insights about human tissue biology and disease – in a way that other, non-human, models such as the mouse cannot. Currently, more than 3,000 scientific articles using brain organoids are published every year. In the past year alone, fundamental insights derived from studying brain organoids at IMBA included the understanding of why the human brain grows to be so large, as well as insight into the human brain’s long-range neuronal connections.
With such strong interest in brain organoids as models for understanding different aspects of the brain, leading experts in the field recently developed a framework for the experimental process. The team, under the leadership of Sergiu Pasca at Stanford University, included Jürgen Knoblich, deputy scientific director of IMBA, who is convinced of this research field’s high potential. “Brain organoids are set to transform our understanding of human development, evolution and disease, and to provide insights we would otherwise not be able to gain.”
Despite the great potential brain organoids hold for research, they do have limitations: Depending on the exact process and protocol in which brain organoids are grown, the composition of the organoid may vary, and certain types of brain cells do not develop in organoids. “Because of these limitations, researchers have a strong interest in setting high standards in the field, also to ensure the reproducibility and transferability of results”, Knoblich adds.
The consensus paper aims to support scientists entering the field, as well as regulatory agencies, in carrying out optimally designed studies, allowing scientists to optimize the experimental model based on the scientific question. The framework, published on March 13 in the print edition of Nature, includes recommendations on the stem cells used as starting points for brain organoids, the process for generating and characterizing the neural cells of interest, the methods for assessing functional properties of brain organoids – including measuring the activity of neurons in the organoids – and, finally, the integration of organoids into neuronal circuits.
“Research using brain organoids is already of exceptionally high quality. Our framework will hopefully accelerate the application of organoids and similar cellular models, allowing us to more quickly realize their potential for neuroscience and its applications”, Knoblich says. “It is testament to the ambitious spirit of brain organoid research that the field’s leading scientists collaborated on this landmark consensus in an extremely communicative and collaborative spirit, setting out a roadmap for how organoid research can maximize its impact on understanding the human brain.”
Sylvia Weinzettl
IMBA- Institut für Molekulare Biotechnologie GmbH
Dr. Bohr-Gasse 3, 1030 Wien
T: +43 1 79044 – 4403
Mail: sylvia.weinzettl@imba.oeaw.ac.at
www.imba.oeaw.ac.at
A framework for neural organoids, assembloids and transplantation studies. Nature. DOI: 10.1038/s41586-024-08487-6
https://www.oeaw.ac.at/imba-de/ueber-imba/newsroom/news/bessere-gehirn-organoide...
Microscope image and artistic representation of the CHOOSE system in a brain organoid.
Knoblich Lab/IMBA
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Microscope image and artistic representation of the CHOOSE system in a brain organoid.
Knoblich Lab/IMBA
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