Introduction of Brain Organoid Development for Psychiatric Disorders

Currently, our understanding of the neurobiology of psychiatric disorders is still limited and biomarker-based clinical management is yet to be developed. The selection of appropriate in vitro models is critical for the discovery of clinically relevant in vitro phenotypes as well as biomarkers. Organoid technology has made advances in understanding neural circuits and neurotransmitters, particularly relevant to understanding psychiatry and psychotropic drugs. Three-dimensional iPSC-derived organoids can reproduce maturation-related features in developing circuits, and brain organoids have been used to model novel neuropathologies in autism and psychotic dissociation.

Fig. 1 Schematic of cerebral organoid and TMT-LC/MS analytical pipeline. (Notaras M, et al., 2021)

Brain Organoid Development Services

Our organoid development platform combines cutting-edge technology with 3D biology approaches to address key challenges in expanding complex psychiatric pathology. We provide end-to-end solutions to standardize the organoid development process from cell culture, processing, and incubation to imaging, analysis, and data processing to deliver accurate study results at scale.

Our brain organoids are cultured from human stem cells and can mimic many aspects of brain development. Their average size is the size of a pea, but within that mass of cells, neurons are growing, making connections, and sending electrical signals to each other. These brain-like organ models can better represent the in vivo environment and thus better predict the potential effects of compounds. This also helps them perform better in toxicology studies because they mitigate the risks associated with false negatives or positives in animal studies.

Our General Steps for Developing iPSC-derived Brain Organoid

• Embryoid body (EB) formation: Inoculation of iPSC cells in 96-well ultra-low attachment plates.
• Germ layer differentiation: Feeding and monitoring EBs.
• Neural induction: transfer to a 24-well plate containing neural induction medium.
• Transfer to Matrigel droplets: Neural ectodermal tissue is transferred to Matrigel droplets.
• Extension of neuroepithelial cell buds: Epithelial extension of neuroepithelial cell buds with fluid-filled cavities.
• Maturation: Tissue is transferred into a rotating bioreactor to promote growth and expansion.

Advantages of Our Organoid

• Intrinsic amplification capabilities: All developmental steps in the tissue can be modeled.
• Scalability and high-throughput capability: Suitable for 384-well plates. This allows it to be used regularly for high-throughput drug screening for efficacy and toxicology studies.
• Versatility: We can adapt the organoid design to present specific functions with a large number of tools.
• Biological relevance: Our organoids can better generalize the constituent cell types and extracellular matrix.

What Can We Help You Achieve in Psychiatry?

• Decoding the impact of genetic variants on pathological brain development leading to psychiatric disorders.
• Investigating a range of novel phenotypes that may be associated with early neurodevelopmental alterations, including diminished responses to electrophysiological stimulation and depolarization, and alterations in growth factor pathways.
• Study of neural circuits and neurotransmitter aspects relevant to understanding psychiatry and psychotropic drugs.
• Study of phenomena and psychiatric disorders related to neural progenitor cell morphology, survival, proliferation, and differentiation.

Ace Therapeutics provides 3D brain organoid development as well as analysis services, including monitoring the size and morphology of developing brain microtissues to help define the size and shape of the tissue. We analyze selected microtissues by confocal imaging at different stages of cellular tissue development by expressing different neuronal markers. If you are interested in this service, please make an inquiry to learn how we can support you in your project.

Reference

1. Notaras M, et al. The proteomic architecture of schizophrenia iPSC-derived cerebral organoids reveals alterations in GWAS and neuronal development factors. Transl Psychiatry. 2021, 11(1):541.