Making lab-grown brain organoids brainier: Using early-stage stem cells is a key to producing structures that are reliable models of disease

By using stem cells to grow miniature brain-like organs in the lab, scientists have opened a new avenue for studies of neurological development, disease and therapies that can’t be conducted in living people. But not all mini-brain organoids are created equal and getting them to precisely mimic the human brain tissues they’re modeling has been a persistent challenge.

“Right now, it’s like the Wild West because there is no standard method for generating mini-brain organoids,” said Bennett Novitch, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and the senior author of a new paper on the topic. “Every neuroscientist wants to make a brain organoid model of their favorite disease, and yet everyone’s organoids do not always look alike.”

In fact, because there is no common protocol for their production and a lack of quality-control guidelines, organoids can vary from lab to lab — and even from batch to batch — which means that a finding made in one organoid may not hold true in another.

“If my lab and another lab down the hall were to conduct drug screens using mini-brain organoid models of the same disorder, we could still get different results,” said Momoko Watanabe, the new paper’s first author and an assistant professor of anatomy and neurobiology at UC Irvine. “We won’t know whose findings are correct because the differences we’re seeing could be reflections of how our models differ rather than reflections of the disease.”

In their new study, published today in Stem Cell Reports, Novitch, Watanabe and their colleagues propose guidelines based on their research that can help scientists overcome two major obstacles standing in the way of these organoids’ full potential: differences in uniformity and structure.

Having organoids that accurately and consistently recreate the structure and cellular makeup of specific sections of the brain is especially important for studying disorders like schizophrenia and autism spectrum disorder in which the brains of affected people often appear identical to neurotypical brains in structure yet exhibit marked differences in function.

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