Scientists have used stem cells to grow miniature human brains in a lab,an advance that can provide new insights into neurological disorders.
The pea-sized brains,that have been “alive” for almost a year,were also used to model microcephaly,a human genetic disorder in which brain size is dramatically reduced.
Scientists at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences grew the complex human brain tissue in a three-dimensional culture system by using pluripotent stem cells that developed into cerebral organoids – or ‘mini brains’ – that consist of several discrete brain regions.
Starting with established human embryonic stem cell lines and induced pluripotent stem (iPS) cells,the group identified growth conditions that aided the differentiation of the stem cells into several brain tissues.
“We modified an established approach to generate so-called neuroectoderm,a cell layer from which the nervous system derives,” said study researcher Juergen Knoblich.
“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 three to four weeks defined brain regions were formed,” Knoblich said.
After 15-20 days,so-called ‘cerebral organoids’ formed which consisted of continuous tissue (neuroepithelia) surrounding a fluid-filled cavity that was reminiscent of a cerebral ventricle.
After 20-30 days,defined brain regions,including a cerebral cortex,retina,meninges as well as choroid plexus,developed.
After two months,the mini brains reached a maximum size,but they could survive indefinitely (currently up to 10 months) in the spinning bioreactor.
Further growth,however,was not achieved,most likely due to the lack of a circulation system and hence a lack of nutrients and oxygen at the core of the mini brains.
While they are not capable of thought or cognition,the mini brains will allow researchers to study aspects of the developing human brain that are difficult to model in animals.
Scientists also created a “mini-brain” from skin cells of a patient with microcephaly. As expected,the patient derived organoids grew to a lesser size.
They found that while the neuroepithilial tissue was smaller than in mini brains unaffected by the disorder,there was increased neuronal outgrowth.
The scientists hypothesised that,during brain development of patients with microcephaly,the neural differentiation happens prematurely at the expense of stem and progenitor cells which would otherwise contribute to a more pronounced growth in brain size.
The study was published in the journal Nature.