Human Brain Organoids Thrive in Mouse Brains

Mouse brains make nice homes for human brain organoids. Brain organoids, also known as mini-brains, are tiny clumps of brain cells grown from stem cells that researchers are using to investigate the neural underpinnings of autism and other neurological disorders. 

But the organoids typically grow in culture for only a few months before they die, limiting their usefulness as models of real brains.Transplanting the three-dimensional clumps of human brain tissue into the brains of mice allows the organoids to continue to develop, sprouting life-sustaining blood vessels as well as new neuronal connections, the new study reports.

The work takes a step toward using brain organoids to study complexities of human brain development and disease that can’t be investigated with current techniques. Brain organoid transplantation may even one day offer a treatment option for traumatic brain injury or stroke.

Gage’s team used human pluripotent stem cells to develop brain organoids, which were grown in culture for 40 to 50 days. Then, the team inserted the organoids into cavities made in mice’s retrosplenial cortex – a region critical for movement and spatial learning. The mice had “humanized” immune systems, Gage says, meaning that their immune cells had been engineered not to attack human tissue.

Around day 5 after transplantation, blood vessels in the organoids could be detected using a fluorescent dye, and by day 14 an extensive network of vessels had grown deep within the human tissue graft. Levels of certain markers in the organoids, such as NeuN+ and PSD95, also showed that the human neural precursor cells were maturing into neurons and forming synapses to connect to each other. At 90 days after implantation, the scientists traced axons extending from the graft deep into the brains of the mice.