Harvard researchers are developing organoids that mimic the cell types and neurological connections in the cerebral cortex.

Researchers have been developing organoids –– miniature human organs –– to support the study of diseases and facilitate drug development. Liver organoids are perhaps most common. Among the organoids that have been developed to date, those that represent the brain have been the least successful – however, that might be changing. Scientists at Harvard University and the Broad Institute report the development of organoids that consistently mimic the cell types and neurological connections in the cerebral cortex, the region of the brain that controls cognition. They plan to use the organoids to learn more about neurological diseases, such as autism and schizophrenia, and the impact that different drugs have on the brain.

The organoids were constructed from stem cell lines (both male and female) grown in the lab for more than six months under conditions designed to lead to the production of the different types of cells found in the cerebral cortex. Cells were grouped by type using information gained from RNA sequencing and big data analysis of gene expression at various stages of brain development.

Importantly, regardless of genetic background, the same cell types were made in the same way and in the correct order in each organoid, yielding brain organoids that were reproducibly accurate models of the human cerebral cortex, according to Silvia Velasco, Ph.D., a research scientist at Harvard and the Broad Institute. These organoids can therefore be used as controls for comparison to brains impacted by neurological diseases.

The scientists plan to use their organoids to investigate autism and are currently using gene editing to develop organoids that can serve as models of the disease.

Other investigators are exploring the development of brain organoids. Tufts University researchers used human induced pluripotent stem cells to build 3D models of the central nervous system, producing cells that could mimic the electrical signals found in the human brain on a collagen and silicon scaffold. The company StemoniX’s microBrain 3D stem cell–based model of the brain will be used by the National Institutes of Health (NIH) to evaluate experimental treatments for opioid addiction and pain.