First mini-lungs, mini-kidneys and mini-hearts and now mini-brains have been grown

Minibrains have been grown from stem cells. They grew 2-3 millimeters (0.08-0.1 in) in diameter, and have survived in lab dishes for 10 months so far. This is the size and has some of the structure of the brain of a 9- or 10-week-old human embryo. Their size is limited, because they lack a circulatory system to provide nutrients and oxygen to their core regions. As a result, the brains could not develop the many layers seen in a real human brain, the researchers said.

Nature – Cerebral organoids model human brain development and microcephaly.

The organoids also lack certain features that human embryonic brains at 9 weeks do have: most importantly, the cerebellum, which is involved in motor movement. Also, the hippocampus, a seahorse-shaped structure crucial for memory, was rarely detected in these brain-like structures.

Researchers used human embryonic stem cells and induced pluripotent stem cells (IPS cells) for this research. Both embryonic stem cells and IPS cells have the ability to turn into any part of the body. But embryonic stem cells are very controversial because in the process of retrieving them for research, the 4- or 5-day-old embryo they are taken from is destroyed. IPS cells don’t come with the same controversy because scientists take a cell — typically a skin cell — then coax it using a chemical bath to revert to a state that resembles a developing embryo.

There did not appear to be an obvious difference between organoids derived from embryonic stem cells and those produced from IPS cells, said Knoblich, also of the Austrian Academy of Science.

Study authors found variability in the organoids they generated; occasionally some of the brain regions they were studying failed to appear.

ABSTRACT – 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.

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SOURCES – Livescience, CNN, Nature

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