King's College London announced on Mar. 27 new research that improves the scalability and reproducibility of neural organoid systems, allowing scientists to study brain development, drug responses, and genetic mutations with greater efficiency.
Neural organoids are lab-grown models that mimic aspects of human brain tissue. They have been used to explore how drugs affect the brain, investigate the impact of specific genetic mutations on neural activity, and study how neural systems develop. However, traditional methods have faced challenges in terms of scalability, reproducibility, and longevity.
The new approach developed by researchers at King's College London addresses these limitations by enabling higher throughput testing over longer periods. Professor Deepak Srivastava said: "Functional genomic and pharmacological studies of neurodevelopment often depend on reliable measures of neuronal function, not just cell identity. Our approach makes it possible to follow neural network activity over time and will allow us and others to directly compare the effects of drugs or gene variants across many parallel cultures."
Traditional three-dimensional (3D) organoids contain a variety of neuron types but can be highly variable from one sample to another, making reproducibility difficult when testing drugs or studying gene function. Two-dimensional (2D) cultures offer easier recording of electrical activity but lack the cellular diversity found in 3D models.
To combine the benefits of both approaches, Dr Adam Pavlinek, Professor Anthony Vernon, Professor Srivastava and their colleagues dissociated cells from multiple 3D organoids into individual neurons before mixing them together on a two-dimensional plate equipped with electrodes known as a microelectrode array. This pooling reduced variability between samples while preserving cell diversity.
Researchers observed developing neurons transitioning from asynchronous firing patterns typical in immature brains to synchronized firing as connections matured over time—something more challenging to monitor in traditional 3D cultures due to technical constraints. The method also allowed scientists to distinguish between technical variability introduced during experiments and biological differences inherent among samples.
Dr Adam Pavlinek said: "The neurons in organoids have a remarkable ability of self-assembling into networks, we think the balance of neuron cell types in these networks may affect their electrical activity and may underlie the differences we see between networks."
