High Hopes from Tiny Brains
Updated: Mar 24, 2021
From a small number of precursor cells and following numerous divisions, migration, and differentiation, the human brain emerges with a unique structural organization critical to its complex functions. Efforts to model this intricate network in vitro have encountered significant bottlenecks. The limited availability of live human brain cells for research has impaired progress toward understanding the mechanisms behind its formation, as well as those leading to psychiatric diseases and other pathologies. Animal models are an excellent resource for understanding the fundamentals of neurodevelopment and neural systems, but most of these models translate poorly to human conditions. Human induced pluripotent stem cells (hiPSC) are being used to fill the knowledge gap between traditional models and human biology and have transformed our ability to make mechanistic inferences about neuropathophysiology, providing the groundwork for more effective pharmacological treatment regimens at the clinic. Differentiation of hiPSCs into NPCs and ultimately mature neural cultures allows for the study of brain development “in-a-dish,” providing a platform with greater accessibility to experimental manipulation. Because these brain organoids mimic human development at the cellular and molecular levels, generation of brain organoids from hiPSCs offers a new, three-dimensional framework for the study of response to chemicals, human brain development, and brain diseases.
The consistent size and functional performance of the StemoniX microBrain 3D platform across independent wells, plates, and lots makes the advanced neural platform ideal for investigating the effect of compounds on both cell viability and neural activity in a highly reproducible fashion. Using indicators of viability (e.g. resazurin or ATP assays) affords the opportunity to investigate compound-induced cell death. While these studies are highly valuable, understanding the nuances of compound impact must be measured by changes in function. Under normal conditions, the functional activity of microBrain 3D spheroids is very regular and robust. Exposure to compound may alter that activity, indicating a change in cellular function, which may be indicative of compound toxicity. The StemoniX neuro team uses microBrain technology to interrogate compound toxicity and modulation of neural activity using both approaches with multiple types of toxic agents – neurodevelopmental, environmental, and end stage. Finally, because microBrain 3D can be created from any individual – healthy or clinical – it can also be used to model neurodevelopmental disorders as well as other genetic and environmentally-induced diseases. microBrains can ultimately serve as predictive pre-clinical translational models for studying disease mechanisms, therapeutic efficacy, and potential compound toxicities. Our efforts are advancing our knowledge of neurological disorders and will continue to push drug discovery to the next level.
StemoniX develops and manufactures hiPSC-derived platforms for pharmaceutical drug discovery, research, and toxicology applications. Our microBrain 3D platform comprises high-density screening plates with a single uniform spheroid per well. Each spheroid is composed of mature cortical neurons and astrocytes and displays spontaneous synchronized neuronal activity readily detectable in the form of calcium oscillations. Our physiologically relevant platforms exhibit features of enhanced cellular maturity, which translates to robust physiological activity, expected responses to known modulators of cellular signaling pathways, and an expanded context of use for target-specific and phenotypic endpoints, elevating performance in toxicity and discovery studies.