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'Mini-brains' grown from stem cells

2 September 2013
Appeared in BioNews 720

Human stem cells have been used to grow miniature brains, 'organoids' that are just millimetres across and at an equivalent developmental stage as in a nine-week-old fetus. The scientists were able to use these structures to model microcephaly, a rare disorder characterised by the development of an abnormally small brain.

The research is the most successful attempt so far to model human brain development in the lab. Similar experiments will hopefully allow increased understanding of neurological disorders and aid the development and testing of new drugs. Until now, studies of human brain development have been difficult due to the organ's structural complexity and the limitations of using animal models that fail to adequately mirror human diseases.

Study leader Dr Juergen Knoblich, from the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences in Vienna, Austria, told the BBC: 'What our organoids are good for is to model development of the brain and to study anything that causes a defect in development. Ultimately we would like to move towards more common disorders like schizophrenia or autism. They typically manifest themselves only in adults, but it has been shown that the underlying defects occur during the development of the brain'.

The team's early studies on the 'mini-brains' suggest that, in the case of microcephaly, the stem cells turned into brain cells too early, instead of first undergoing the many rounds of cell division that produce a normally-sized brain.

Lead author Dr Madeline Lancaster told The Guardian: 'When I looked at the organoids derived from the microcephaly patient cells, the immediate thing I noticed was that [their] overall size was much smaller than the organoids derived from control, healthy cells'.

The researchers, from the IMBA and the University of Edinburgh, UK, used established human embryonic stem cell lines and induced pluripotent stem cells derived from skin cells in their work.

By recreating conditions similar to those during development, they were able to generate a cell layer equivalent to the 'neuroectoderm', a tissue which, in the embryo, gives rise to the brain and spinal cord. After several months, cultured fragments of this tissue formed 'cerebral organoids', spherical structures measuring approximately four millimetres in diameter.

These 'mini-brains' organised into defined regions resembling those in the developing brain, although further growth was not possible, most likely due to the lack of a circulatory system to supply oxygen and nutrients to their core.

Speaking to the BBC, Dr Zameel Cader, a consultant neurologist at the John Radcliffe Hospital in Oxford, said that some of the similarities with a human brain were 'really quite astounding'. Dr Cader, who was not involved in the study, emphasised that the organoids were 'a long way from conscience or awareness or responding to the outside world'.

Dr Knoblich also added that the aim of the work was not to grow replacement brain parts in culture. 'The ultimate complexity of the brain will not allow any replacement of structures', he told The Guardian. 'In the adult brain all the parts are intimately integrated with other areas of the brain. It would be very hard to repair defects with this'.

The study was published in the journal Nature.

Brains on Demand
Institute of Molecular Biotechnology (press release) |  28 August 2013
Cerebral organoids model human brain development and microcephaly
Nature |  28 August 2013
Miniature brains grown in test tubes - a new path for neuroscience?
The Guardian |  28 August 2013
Miniature 'human brain' grown in lab
BBC News |  28 August 2013
Scientists grow mini brains from stem cells
CNN |  28 August 2013
Stem Cells Mimic Human Brain
Scientific American |  28 August 2013
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