Industrial-Scale Mini-Brains: Simple Trick Could Transform Brain Research

Stanford scientists have discovered that a common food ingredient, xanthan gum, can solve a major challenge in brain research. Using this additive, they were able to mass-produce lab-grown “mini-brains,” called organoids, that mimic parts of the human brain. This paves the way for better studying diseases like autism and epilepsy and even safely testing the effects of hundreds of medications on brain development.

In recent years, scientists have developed a revolutionary tool for studying the human brain: cerebral organoids. These organoids are small, three-dimensional structures created in the laboratory from human stem cells that can organize themselves in a manner similar to brain tissue.

In practice, they function as “mini-brains” that mimic important aspects of neuronal development and activity. This allows researchers to investigate how the brain forms, where certain neurological diseases arise, and even how new medications might affect the nervous system, without having to resort to direct experiments on human or animal brains.

Despite the enormous potential, there was a problem hampering the advancement of this field: organoids, when cultured in suspension, tended to fuse with one another. This made it very difficult to produce large quantities of standardized organoids with similar size and shape, which is crucial for ensuring reliable results in research and drug testing. In other words, if each organoid grows differently, experiments become imprecise.

The solution found was surprisingly simple and inexpensive: a very common food additive called xanthan gum. This polysaccharide, widely used to add consistency to sauces, creams, and other products, increased the viscosity of the liquid in which the organoids were grown.

This prevented the organoids from sticking together and allowed them to develop independently and uniformly. Most impressively, this substance did not alter the organoids' biological characteristics at all; they continued to exhibit the same neuronal organization, morphology, and even functional activity.

The technique was developed by an interdisciplinary team at Stanford University, within the Stanford Brain Organogenesis Program, affiliated with the Wu Tsai Neuro Institute.

The two main leaders were: Sergiu Pasca, Professor of Psychiatry and Behavioral Sciences at Stanford, a pioneer in the use of brain organoids to study neurodevelopmental diseases, and Sarah Heilshorn, Professor of Materials Engineering at Stanford, a biomaterials expert who helped test different substances until identifying xanthan gum as the ideal solution.

Sergiu Pasca, Kenneth T. Norris Jr. Professor of Psychiatry and Behavioral Sciences at Stanford School of Medicine and the Uytengsu Family Director of the Stanford Brain Organogenesis Program. Credit: Stanford University

They and their team tested 23 biocompatible materials and found that xanthan gum, a simple and inexpensive food additive, solved the problem of organoid fusion, enabling mass production with quality and standardization.

Thanks to this discovery, scientists were able to produce organoids on a massive scale: thousands of them at a time. This opened the door to much more ambitious experiments, such as screening hundreds of drugs already approved by the FDA (the United States regulatory agency).

Sarah Heilshorn, Rickey/Nielsen Professor at the School of Engineering. Credit: Stanford University

In one study, more than 2,400 cortical organoids were exposed to 298 different substances to assess their effects on the development of the "mini-brain." The results showed that some drugs actually hindered the growth of the organoids, raising concerns about potential risks to the developing brain, especially in pregnant women and babies.

Besides improving the safety of medication prescriptions, this technique has enormous implications for science. With large-scale, standardized organoids, it becomes possible to investigate, in much greater detail, how disorders such as autism, epilepsy, and schizophrenia arise, as well as to test new treatments.

Differences between control organoids without xanthan gum (hCO), showing a cluster between them, and those treated with the gum (hCO + XG), showing no clusters and greater quantities.

Another advantage is that the methodology has been published as open access, allowing any laboratory in the world to reproduce the method at no additional cost, accelerating global scientific collaboration.

In short, something as simple as a food thickener has become the key to solving one of the biggest obstacles in the mass production of brain organoids. This innovation not only transforms the way scientists study human brain development but also paves the way for discoveries that could radically change the understanding and treatment of neurological diseases.

READ MORE:

Scalable production of human cortical organoids using a biocompatible polymer

Genta Narazaki, Yuki Miura, Sergey D. Pavlov, Mayuri Vijay Thete, Julien G. Roth, Merve Avar, Sungchul Shin, Ji-il Kim, Zuzana Hudacova, Sarah C. Heilshorn, and Sergiu P. Pașca

Nature Biomedical Engineering. 27 June 2025

DOI: 10.1038/s41551-025-01427-3

Abstract: 

The generation of neural organoids from human pluripotent stem cells holds great promise in modelling disease and screening drugs, but current approaches are difficult to scale due to undesired organoid fusion. Here we develop a scalable cerebral cortical organoid platform by screening biocompatible polymers that prevent the fusion of organoids cultured in suspension. We identify a cost-effective polysaccharide that increases the viscosity of the culture medium, significantly enhancing the yield of cortical organoids while preserving key features such as regional patterning, neuronal morphology and functional activity. We further demonstrate that this platform enables straightforward screening of 298 FDA-approved drugs and teratogens for growth defects using over 2,400 cortical organoids, uncovering agents that disrupt organoid growth and development. We anticipate this approach to provide a robust and scalable system for modelling human cortical development, and facilitate efficient compound screening for neuropsychiatric disorders-associated phenotypes.