Human brain tissue has been successfully developed in an Austrian laboratory. The new method allows stem cells to develop into mini brains that consist of several discrete brain regions.
Article continues below
Instead of using so-called patterning growth factors to achieve this, scientists at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences (OeAW) fine-tuned growth conditions and provided a conducive environment.
As a result, intrinsic cues from the stem cells guided the development towards different interdependent brain tissues. Using the "mini brains" (cerebral organoids), the scientists were also able to model the development of a human neuronal disorder and identify its origin, thus opening up routes to long hoped-for model systems of the human brain.
The development of the human brain remains one of the greatest mysteries in biology. Derived from a simple tissue, it develops into the most complex natural structure known to man. Studies of the human brain's development and associated human disorders are extremely difficult, as no scientist has thus far successfully established a three-dimensional culture model of the developing brain as a whole.
Now, a research group lead by Dr. Jürgen Knoblich at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) has changed just that.
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.
While using media for neuronal induction and differentiation, the group was able to avoid the use of patterning growth factor conditions, which are usually applied in order to generate specific cell identities from stem cells.
Dr. Knoblich explains the new method: "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 three to four weeks defined brain regions were formed."
Already 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.
The new method also offers great potential for establishing model systems for human brain disorders. Such models are urgently needed, as the commonly used animal models are of considerably lower complexity, and often do not adequately recapitulate the ■