ÖAW/IMBA: Building better brain organoids: A new framework for researchers
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. 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 replicating specific timepoints and sections of the brain, such as of early embryonic development or cortical neurons.
As brain organoids mimic aspects of the brain’s physiology, organoids hold the potential to reveal new insights about human tissue biology and disease. Currently, more than 3,000 scientific articles using brain organoids are published every year – in the past year, 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 was the first to use cerebral organoids for modelling brain disease. This 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 December 9 in 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.
“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”, Jürgen Knoblich says. “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.”
Publication:
A framework for neural organoids, assembloids and transplantation studies. Nature. DOI: 10.1038/s41586-024-08487-6