Friday, 30 August 2013

Growing mini brains

Lancaster MA et al. Cerebral organoids model human brain development and microcephaly. Nature (2013) doi:10.1038/nature12517

The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.


An "organoid" showing different brain regions, all cells are in blue, neural stem cells in red, and neurons in green. In a real brain most of the tissue would be nerves

iPS cells are induced pleuripotent stem cells, which means that they can take any cell and revert it back to a stem cell which is capable of becoming any type of cell.With the right mix of nutrients and a little bit of coaxing, human stem cells derived from skin can assemble spontaneously into brain-like chunks of tissue called the mini brains and a step closer to artificial brain. 

The stem cells were grown on a gel that resembled natural connective tissues found in the brain and then infused it with nutrients and oxygen using a spinning culture. The mini brains developed distinct brain regions and functional electrical activity.

Hear the scientists here (Click)

Under a microscope, researchers saw discrete brain regions that seemed to interact with one another. But the overall arrangement of the different proto-brain areas varied randomly across tissue samples — amounting to no recognizable physiological structure and lacked blood vessels. They only grew to 3-4 mm in as much as ten months. They did the same from someone who had a genetic condition that meant they had a small brain and the chunks grow less.

We have been growing nerves, and myelinating cells and microglia and astrocytes in 3D structures, but it is technically challenging and a slow laborious process for hunting for remyelinating cues. This new study is the beginning of an exciting process, but it is just the beginning. 
However, there are other implications also.


To do work on animals, researchers have to jump through hoops and go through a lot of red tape and get ethical approval to do experiments. 

You may be interested to know that scientists working on cell cultures do not and often do not need ethical approval for their work. 

This is perhaps a shame as sometimes there is a load of old tosh coming out of some labs that solely focus on cell culture. 

Once an animal is dead is is not protected by the laws that protect living animals that are used in research. 

Each year you hear how many animals are used in research. However, this is a fudge and a massive under-representation because many animals that are killed for tissues do not need to be reported.

In neuroscience, this often may mean foetal or neonatal (freshly-born) animals are used e.g. to study myelination because they can be used to grow nerves and myelinating cells more easily as development in ongoing in these animals. e.g. Mice have little myelin on their nerves when they are born. 

However, with the ability to grow human cells into brain tissue then becomes a very strong ethical argument against using animals for research in cell cultures. Why use a model when you can use the real thing? With iPS cells you could grow the brain tissue from MSers. 

Yes it will be expensive to grow the human cells, but the cost-saving exercise has not been a valid reason to do living animal experiments when there is an alternative from the ethical standpoint. It is perhaps time that everybody using animal tissue, live or dead go through a full ethical review.  

Maybe in your country they do already

2 comments:

  1. "They did the same from someone who had a genetic condition that meant they had a small brain and the chunks grow less."
    They also added a normal copy of the defective gene and the chunks grew to normal size. Brilliant!

    ReplyDelete
  2. I like it that MD2 checks out the fine detail of the postshe is the QC (quality control)

    ReplyDelete

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