Article

December 2015

‘Mini-brains’ in a Dish: Unlocking the Mysteries of Human Brain Development

Video - December 2015

‘Mini-brains’ in a Dish: Unlocking the Mysteries of Human Brain Development

With a rapidly aging population, age-related neurodegenerative diseases are becoming a major issue of public health worldwide. Although mouse models have proven invaluable to identify mechanisms for a variety of diseases, the complexity of the human brain has made it difficult to study brain disorders in model organisms.

Scientists at the Institute of Molecular Biotechnology (IMBA) in Vienna (Austria) have now overcome these limitations and devised strategies to grow miniaturized versions of the human brain in a dish. Starting with samples of skin cells, scientists can readily convert these cells into induced pluripotent stem (iPS) cells – adult cells reprogrammed to behave like embryonic stem cells. Using a combination of growth factors, small molecules and three-dimensional culture conditions, they can then coax iPS cells to organize into complex neural tissue clumps. Curiously, these ‘cerebral organoids’ recapitulate many features of human embryonic brain development, making them attractive models to study how networks of living human brain cells develop and function in unprecedented detail.

Beyond basic research, brain organoids represent a big step towards creating a platform to study the genetic underpinnings of neural disorders. In organoid cultures, scientists can now rapidly test how developing neurons are affected by various drug compounds or genetic modifications. Furthermore, since these ‘mini-brains’ can also be grown from patient-derived cells, organoids serve as unparalleled and accurate models for a wide range of neurological diseases.

Juergen Knoblich and colleagues (IMBA, Vienna) initially used the system to model key aspects of microcephaly, a condition that causes severely stunted brain growth and cognitive impairment. Similar to the clinical manifestations, the researchers found that patient-derived organoids also showed substantial growth defects in culture. The ease of genetic manipulation in cultured organoids then allowed Knoblich to trace this effect to the premature differentiation of neural stem cells, thereby essentially depleting the population of progenitor cells that fuels normal brain growth.

These studies pave the way for promising new approaches to identify the mechanistic basis of age-related neurodegenerative disorders. In addition to Parkinson’s and Alzheimer’s disease, brain organoids could help unlock the mysteries of schizophrenia, epilepsy, autism and post-traumatic stress disorder, which affect millions of people worldwide. They also open up possibilities for personalized medicine: Scientists and clinicians could use brain organoids to study how individual patients react to particular treatments or newly developed drugs. Therefore, ‘mini-brains’ could serve as a testing ground for therapies and could help doctors decide on the best treatments for individual patients.

References:

http://www.nature.com/nprot/journal/v9/n10/abs/nprot.2014.158.html

Image credits: Cross-section of human cerebral organoid, stained with markers for neural progenitors (red) and mature neurons (green). Lancaster et al., Nature

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