A groundbreaking study published in Nature on June 26 by a research team from Harvard University has unveiled a novel approach to brain development and drug testing. By cultivating a 3D brain model using stem cells from multiple donors, this research offers new insights and evidence for understanding brain development and drug responses, potentially paving the way for advancements in brain research and protection.

Creation of the Multi-Donor Cultivated 3D Brain Model

Given the slow growth of brain organoids, combining stem cells from multiple donors into a single organoid is a method to address this issue. Previously, multiple donor cell clusters were used mainly for their ease of handling and the ability to discover a wide range of human genetic diversity within a single model. However, the challenge lies in the inconsistent growth rates of the initial stem cells, which can lead to faster-growing cell lines dominating the system.

According to the Nature article, Harvard's Paola Arlotta and her research team have solved this problem. Arlotta revealed that the key issue was maintaining consistent growth rates among initial stem cells. By creating individual organoids from single donors and allowing them to mature, the growth rates of organoid cells gradually became similar. At this stage, these structures were mixed and continued to grow together, resulting in a composite organoid. After three months of growth, the composite organoid expanded to 3-5 millimeters, containing cell types identical to those in fetal cortical tissue. Additionally, after one month, organoids formed from the stem cells of five donors exceeded 1 millimeter in width. This cultivation method has produced a robust 3D brain model.

Applications of the Multi-Donor 3D Brain Model

Previously, teams had developed 2D slices containing brain cells from multiple donors. Like these 2D chimeras, the 3D brain model helps scientists understand how drugs affect different individuals. The research team used the 3D brain model to test neurotoxic drugs, determining the variation in drug effects based on the number of different donor cell lines.

Results showed that the model, when combined with the antiepileptic drug valproic acid, demonstrated faster growth in a donor cell line that had been artificially reduced. This indicates that the model can effectively test the impact of drugs on different individuals.

Future Prospects for the Multi-Donor 3D Brain Model

Currently, the composite organoid includes stem cells from only five donors. However, given the method's effectiveness, it is foreseeable that future models could incorporate stem cells from hundreds of individuals. This could lead to more precise and rapid predictions of individual responses to new therapies, providing research teams with new avenues for improving treatments.

Nonetheless, some experts urge caution in the study of chimeric models. Robert Vries, CEO of HUB Organoids in the Netherlands, emphasized the need to ensure that the observed effects in chimeric models are due to the drug's impact on specific cell lines, rather than interactions between different cell types.

Indeed, this research is still in its early stages, and many observed results remain unclear. This presents an opportunity for teams in the field to further investigate and understand these phenomena.


  1. Antón-Bolaños, N., Faravelli, I., Faits, T. et al. Brain Chimeroids reveal individual susceptibility to neurotoxic triggers. Nature (2024).