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Growing Functioning 3D Brain Tissue from Stem Cells

3D brain cells

Image credit: Cells displaying Purkinje cell markers. Credit: RIKEN

The primary aim of study on stem cell is targeted at creation of functional replica tissues and organs to be used as replacements in case of disease or injury, or for further development of drugs as well as other kinds of therapeutic techniques. Although it has been challenging to get tissues to be grown in the laboratory in three dimensions in the field, it is quite doubtful for structures to do so in the nervous system. While having the neurons to grow at all, they should be connected in a very special way so as to work properly. A big move has been made on this front by a group of scientists of RIKENCenter for Developmental Biology in Japan. According to the report in Cell, the team has succeded in growing 3D functional brain tissue with proper patterns.

With the brain tissues being grown from human embryonic stem cells, more growth factors were taken in series during the developmental process. The first one was regarded as basic fibroblast growth factor 2(FGF2), which were very important for the development, wound healing as well as tumor growth. In the initial period of three weeks, the cells started to differentiate into midbrain and hindbrain regions. In the following two weeks, the epithelial cells leading to the cerebellum took shape in the hindbrain. In addition, such cells showed precursors to certain neurons which were exclusive to the cerebellum, like Purkinje cells that was helpful in regulation of motor movement and granule cells, which had presented a lot of functions.

Furthermore, the scientists had incorporated FGF19 in the second week and discovered that it could give rise to indications of dorsal-ventral (top-bottom) patterning within 21 days. During the 4th week of cultivation, stromal cell-derived factor 1 (SDF1) was given, thus creating the proper dorsal-ventral polarity in the growing brain structure. As for the dorsal region, SDF1 could give rise to the development of areas, which would generate Purkinje, deep cerebellar projection neurons and the rhombic lip. These are fundamental for developing and migrating granule cells.

After fifteen weeks in culture, the cells with treatment of FGF2 demonstrated extra markers for Purkinje cells, apart from starting to show their own physical properties and basic electrophysiological function. The granule cells were also getting more mature with the obvious sign of normal cell migration. The developing neuronal cells could be even able to grow in the proper orientation to one another.

The self-patterning of cells observed in this research was something similar to what could be expected during the first three months of embryonic development, although the recreation was incomplete. It is hoped that this would be refined in the days to come so as to improve what could be done in the period of the first three months. Hopefully, In the end, the scientists could identify a method regarding the long-term culture of the brain tissue through the end of the second three months.

Talking of the current study, Keiko Muguruma, the lead author said, the principles of self-organization demonstrated in their research were vital for developmental biology in the future. It had been successful in trying to produce the cerebellum from human iPS [induced pluripotent stem] cells. As a result, such patient-derived cerebellar neurons and tissues would be quite useful for modeling cerebellar diseases, for example, the spinocerebellar ataxia.

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