Brain organoids created from human embryonic stem cells offer scientists a powerful way to study the developing brain in three dimensions. However, organoids need nutrients and oxygen carried in blood to thrive, just as a developing fetal brain does. Now Yale researchers have developed a method to induce growth of blood vessels in organoids and prevent the death of cells, which has hindered efforts of scientists studying brain development, they report October 7 in the journal Nature Methods.

“The introduction of vasculature will hopefully lead to our ability to create larger, healthier organoids,” said In-Hyun Park, associate professor of genetics and associate professor in the Child Study Center and Yale Stem Cell Center.

The development of organoids, created by spurring development of human embryonic stem cells, has been a boon to neuroscientists studying the origins of neurodevelopmental diseases such as autism and schizophrenia, which can arise from abnormalities that form early in brain development. Although just a few millimeters in diameter, organoids offer a new window into how developing regions interact in real time.

However, organoids are also prone to widespread death of cells caused by a lack of blood vessels, particularly within the interior of the developing organ. Park’s lab overcame that problem by inducing the expression of hETV2, a gene associated with the creation of vasculature in the developing embryo, within human embryonic stem cells. Its studies, led by Bilal Cakir and Yangfei Xiang, found that cell death in the organoids with engineered cells dramatically decreased, but that new blood vessels were created when the organoids were transplanted into a mouse.