Guidelines for Human Brain Organoid Transplantation Needed

As research involving the transplantation of human "mini-brains—known as brain organoids—into animals to study disease continues to expand, so do the ethical debates around the practice. A paper published today in Cell Stem Cell by researchers from Penn Medicine and the Department of Veterans Affairs sought to address this dilemma by clarifying the abilities of brain organoids and suggesting an ethical framework that better defines and contextualizes these organoids and establishes thresholds for their use.

"Due to their ability to mimic certain brain structures and activity, human brain organoids—in animal models—allow us to study neurological diseases and other disorders in previously unimaginable ways," said the study's first author H. Isaac Chen, M.D. "However, the field is developing quickly, and as we continue down this path, researchers need to contribute to the creation of ethical guidelines grounded in scientific principles that define how to approach their use before and after transplantation in animals."

Lab-grown brain organoids—which are derived from human pluripotent stem cells and grown to a size no bigger than a pea—can recapitulate important brain architecture and several basic layers of the human cortex. Some resemble the midbrain, hippocampus, and the hypothalamus, and have genetic similarities to the human brain.

Still, today's brain organoids remain distinctly different from the actual human brain, the authors note. Their maximum size remains small due to inadequate nutrient, gas, and waste exchange, which limits development. Organoids also lack endothelial cells, microglia cells, and other cell types that contribute to the brain's microenvironment. Furthermore, organized structural nodes and the white matter connections among these cells are absent, which are both necessary for higher brain function.

Work on developing a "better" brain organoid continues to make strides, but although the question of the host animal becoming more "human" remains a concern, there is not cause for immediate worry. "Current brain organoid transplantation is more likely to worsen brain function than improve it," the authors wrote, "because transplantation involves the creation of a surgical cavity that likely leads to loss of function and a lack of connectivity." The authors also note that transplantation of brain organoids is only impactful in local areas where immediate connections are made, which means it's unlikely to generate brain functions across many brain regions, like consciousness.