Complex human ‘mini-brains’ successfully grown from stem cells

Scientists have successfully grown complex human brain tissue from stem cells using a new 3D culture system, according to a study published in the journal Nature.

Researchers from the Institute of Molecular Biotechnology (IMBA) at the Austrian Academy of Sciences (OeAW) say the newly created tissue could be the start of developing model systems for the human brain.

The scientists began the research by using established human embryonic stem cell lines and induced pluripotent stem (iPS) cells from mouse embryonic fibroblasts. They identified growth conditions that helped the stem cells differentiate into a variety of brain tissues.

The researchers used “media” for neuronal induction and differentiation, which allowed them to avoid “patterning growth factor conditions.” They say that these conditions are usually applied to generate particular cell identities from stem cells.

Dr. Jürgen Knoblich from the IMBA and lead study author explains the process:

“We modified an established approach to generate so-called neuroectoderm, a cell layer from which the nervous system derives. Fragments of this tissue were then maintained in a 3D-culture and embedded in droplets of a specific gel that provided a scaffold for complex tissue growth.”

“In order to enhance nutrient absorption, we later transferred the gel droplets to a spinning bioreactor. Within 3 to 4 weeks, defined brain regions were formed.”

A cross-section of a ‘mini-brain’ showing development of different brain regions. Cells are blue, neural stem cells are red, and neurons are green.

Copyright: IMBA/Madeline A. Lancaster

‘Mini-brains’ grown after 2 months.

“Cerebral organoids” formed after 15-20 days. These organoids had continuous tissue (neuroepithelia) around a fluid-filled cavity similar to a cerebral ventricle – a cavity in the brain that is continuous with the central canal of the spinal cord.

Defined regions of the brain – including a cerebral cortex, retina, meninges and a choroid plexus – developed after 20-30 days.

After 2 months, full size “mini-brains” had been created that have continued to survive in a spinning bioreactor, and they are currently surviving at 10 months.

The study authors say:

“We have established a novel approach to studying human neurodevelopmental processes through in vitro culture of cerebral organoids from human pluripotent stem cells.