When you can’t use the real thing, many times a model of it will do. When it’s in the lab, for biology and medical research, models of living organs, or “organoids” as they are called, are used when it isn’t possible to experiment with actual human organs. They are especially important in neuroscience research. Because the brain is complex and it isn’t always ethical to use human tissue, there has been much effort directed at creating or growing 3D “mini brains.” There are already 2D models of brain tissue in used at many labs, but adding the 3D feature has been a challenge.
Mini-brain organoids are created with stem cells. Just as in human development, these cells are the building blocks of the brain and nervous system.. Researchers at the Salk Institute have recently published the results of their efforts toward the goal of creating a 3D tissue model of the brain. Appearing in the journal Cell Reports, their study could lead to a better grasp of brain development as well as neurological diseases like dementia and mental illness. The 3D mini-brains they were able to produce are much more similar in structure and function to the 2D models currently available.
Joseph Ecker, senior author of the study and a Howard Hughes Medical Institute Investigator and professor and director of Salk’s Genomic Analysis Laboratory stated, “Being able to grow human brain cells as miniature three-dimensional organs was a real breakthrough. 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.”
Research into creating models of tissue in the lab has been focused on cell biologists who are using embryonic stem cells in a lab dish and hoping to coax them into differentiating in to separate types of brain cells. The problem is that the human brain consists of layers upon layers of cells and these flat petri dishes of cells had limited benefit for medical research. Scientists in Europe were able grow brain cells encased in 3D gel, but it wasn’t known until the recent research from the Salk Institute how well these “cerebral organoids” or COs would work.
In a collaboration with the European lab that developed the method for lab grown COs, Ecker’s lab compared the early brain development of the COs to real brain tissue at the same developmental stage. They did this by using age-matched real tissue from the National Institutes of Health NeuroBioBank and 2D brain-model data from various other studies. They found that the 3D COs were much more like real brain tissue than 2D models in the degree of differentiation the cells achieved and in their gene expression. They did not, however, reach the same level of maturity.
Another significant finding was that both the 3D and 2D cell models had similar patterns of aberrant growth. That is common in any tissue that is lab-grown versus part of an actual human brain, but the fact that the cell patterns went awry in much the same way could help researchers learn even more about to make models as close to the originals as possible. Juergen Knoblich, co-senior author of the new paper and head of the European lab explained, “Our work demonstrates the remarkable degree to which human brain development can be recapitulated in a dish in cerebral organoids.” Check out the video below to see some of this cutting edge brain creation for yourself.