Stem cell ‘mini-brain’ very similar to real brain

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BUILDING a realistic model of the human brain is a crucial part of understanding brain development, as well as neurological disorders such as Alzheimer’s or Parkinson’s disease. Using human stem cells, researchers have created a 3-D model of the human brain – and new research investigates how similar it is to a real brain.
A new study assesses the functionality of a 3-D brain model, shown here in a fluorescent cross-section. Currently, scientists typically use 2-D brain models. Latest developments in brain modeling, however, include creating functional 3-D brain-like tissue and entire “mini-brains” from human stem cells. New research investigates such a 3-D mini-brain model and examines its advantages over a 2-D brain model.
The study was carried out by scientists at the Salk Institute, and the findings were published in the journal Cell Reports. The ability to grow a brain entirely out of human cells is not new, but it is quite recent and has been hailed by the authors of this new study as “a real breakthrough.” Salk Institute researchers cite the 2013 European study, in which scientists grew a cerebral organoid (CO) model in vitro from embryonic and adult stem cells. Researchers then placed the cells in a 3-D gel, where they developed into realistic layers that reflected an actual human brain.
Before that, embryonic stem cells had been transformed into single-layered brain cells inside a petri dish, but this had the obvious limitation of being 2-D instead of the 3-D real brain. Limited 2-D brain models are widely used today, but Salk Institute researchers point to the advantages of 3-D CO models.
“Being able to grow human brain cells as miniature three-dimensional organs was a real breakthrough,” says Joseph Ecker, the senior author of the new study, a Howard Hughes Medical Institute Investigator, and professor and director of Salk’s Genomic Analysis Laboratory. “Now that we have a structurally realistic model, we can start to ask whether it is also functionally realistic, by looking at its genetic and epigenetic features.” Assessing genetic and epigenetic features of mini-brains
led by Ecker compared early development COs with real brain tissue at the same early developmental stage. The team created COs for their analysis using a human embryonic cell line called H9. They chemically induced the cells into a neurodevelopmental pathway for 60 days. Then, researchers analyzed the mini-brains’ epigenetics, looking at the patterns of chemical markers that are responsible for activating or silencing genes.

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