A laboratory-grown brain may sound closer to sci-fi than reality, but over the past decade, research institutes have successfully grown small models of the human brain known as brain organoids. Brain organoids are only a few millimeters long, certainly not the size of a fully developed brain, but they are composed of millions of cells and share the same basic structure as the human brain. The first successful brain organoid was reported in 2013, and since then, brain organoid research has experienced significant growth, with over 13,798 citations in 2022. As brain organoid research begins to make its mark in research and healthcare, time will tell if they represent a lasting advancement or a passing phase. 

Neuroscience research is grounded in models. A model allows researchers to understand how a disease affects the brain and is a potential platform for testing new drugs and treatments. A research team at the Austrian Academy of Sciences notes that neurological diseases have been studied primarily through animal models, such as the house mouse. Mice models, however, have inherent limitations due to the discrepancies between the mouse and human brains. For example, the human brain has a greater surface area, connectivity, and unique structural components, which explain why some disorders do not appear and cannot be studied in mice.

While no model perfectly replicates the human brain, brain organoids are a step up from animal models and may serve as an intermediate between animal and human trials. However, brain organoids are not meant to replace animal models entirely. For example, when testing the effects of turning a gene on and off, researchers can use organoids to model the specific mechanisms in the human brain and animal models to understand the behavioral implications of altering the aforementioned gene. In this way, the two models can complement each other, accounting for the other's limitations.

A research group at Harbin Medical University explains the procedure for brain organoid generation. Culturing a brain organoid is a multi-step process that starts with pluripotent stem cells (PSCs). 

Stem cells are a type of cell that can divide and differentiate into specialized cells, like cardiac, nerve, or blood cells. “Pluripotent” refers to the high degree of differentiation the cell can undergo.  The PSCs then aggregate together to form bodies named embryoid bodies (EBs). After approximately a month of culturing, the EBs differentiate into various brain regions, which can then be studied.

The primary use of a brain organoid model comes from organoids that model disease. These organoids can be created by editing the genes of a healthy brain organoid, infecting a healthy brain organoid with a virus, or using PSCs from donors with neurological disorders. Researchers will then compare abnormal and healthy brain organoids to study how abnormalities develop and test potential cures. 

An example of a successful brain organoid study was led by Mr. Cleber A Trujillo, who studied Rett Syndrome. This debilitating neurodevelopmental disorder causes a severe loss of coordination, speech, and motor skills, and currently has no cure. Trujillo used hPSCs from patients with healthy brains and patients with Rett syndrome to grow control and experimental brain organoids. He and his team then tested several drugs on the organoids and found two drugs that help reverse the issue on a cellular level [6]. If these drugs pass through clinical trials on patients, they may be the first treatment for Rett Syndrome. Trujillo is one of the many researchers using organoids as disease models. As of 2022, brain organoids have been used to model diseases that cause structural defects, infectious diseases, neurodegenerative diseases, neurodevelopmental disorders, and brain tumors. Organoids were even used to model SARS-CoV-2, the virus that causes coronavirus. 

The potential for brain organoids is promising for medical professionals, patients, and researchers alike. While the full extent of brain organoids is still being researched, the concept of laboratory-grown brains is an exciting avenue for research and medicine. With studies like Trujillo's, brain organoids may help us cure diseases and better understand the body's most mysterious organ: the human brain.