Whole-brain organoid mimics brain of 40-day-old fetus

Organoids comprising brain and blood vessel cells have been generated from human pluripotent stem cells, yielding a composition of different cell types similar to that of a 40-day-old fetus.

A new type of brain organoid, which accurately mimics the interaction between different types of neural cells and basic versions of blood vessels in the brain, has been developed by researchers at Johns Hopkins University, Baltimore, Maryland. The group separately generated cerebral, mid/hindbrain and endothelial (blood vessel) organoids from human induced pluripotent stem cells, and then combined the different types of organoids using special sticky proteins.

'Most brain organoids that you see in papers are one brain region, like the cortex or the hindbrain or midbrain. We've grown a rudimentary whole-brain organoid; we call it the multi-region brain organoid (MRBO),' said Dr Annie Kathuria, lead author of the study published in Advanced Science.

Organoids are small, three-dimensional replicas of organs, usually grown from pluripotent stem cells. MRBOs contain cerebral, midbrain, hindbrain and blood vessel cell types, which could allow study of the interaction between the blood vessels and neural cells in the brain. The researchers emphasise that MRBOs are not conscious and are considerably smaller than a human brain, although they did show some electrical activity and the formation of a rudimentary blood-brain barrier.

'Diseases such as schizophrenia, autism, and Alzheimer's affect the whole brain, not just one part of the brain. If you can understand what goes wrong early in development, we may be able to find new targets for drug screening,' said Dr Kathuria.

Neurological conditions affect more than one billion people worldwide and are difficult to study as they often involve multiple different regions and cell types within the brain. For example, schizophrenia and some types of autism are thought to involve the brain's vascular system as well as neural cells. As the MRBOs developed in this study include vascular cells, they could provide the opportunity to study and better understand these conditions.

'We can test new drugs or treatments on the organoids and determine whether they're actually having an impact on the organoids' Dr Kathuria added.

She and her colleagues hope that MRBOs could help to reduce the 96 percent failure rate for neuropsychiatric drugs in Phase I clinical trials as they provide a complex human-specific model, rather than the animal or simple human cell models currently used. There is also potential for patient-specific organoids to be developed, which could be used to determine the most effective treatment for each patient.