Welcome to our first MaxWell Monthly Must-Reads blog of 2023! After 2022 – a year full of great scientific advances and discoveries – this month we would like to focus on induced Pluripotent Stem Cells (iPSC) as a great tool for Disease Cell Modelling and for developing novel disease therapies.
Development and advancement of patient derived iPSC technology has opened several avenues for scientists to generate relevant and reproducible human in vitro models. iPSC technology has also allowed researchers to better understand disease mechanisms at a cellular level as well as allowing for screening and testing drug candidates on specific cell types.
High-Density Microelectrode Array technology (HD-MEA) offers a powerful tool to study the activity of individual neurons or neuronal networks. The combination of HD-MEA and iPSC technology offers a novel platform to study human neuronal activity not only at a cellular but also subcellular level.
This month, we are highlighting one publication and one application note that showcase the potential of combining iPSC and HD-MEA technology for disease modelling and drug discovery.
Recently, Danny McSweeney and colleagues (McSweeney et al., 2022, iScience) published a study on a neurodevelopmental disease-associated protein kinase called CASK (Calcium/Calmodulin Dependent Serine Protein Kinase), involved in the regulation of neuronal maturation and synaptic function in human induced cortical excitatory neurons. Mutations that cause loss-of-function in CASK results in severe developmental phenotypes such as microcephaly with pontine and cerebellar hypoplasia, X-linked intellectual disability, and autism, indicating the importance of elucidating the molecular and cellular mechanisms underlying such CASK-related syndromes. In this study, the MaxOne HD-MEA system was utilised to assess the neuronal network activity of CASK induced iPSC derived cortical neurons, revealing insights on the compromised network connections & synchronicity compared to wild-type neuronal morphology & synaptic formation.
CASK loss of function differentially regulates neuronal maturation and synaptic function in human induced cortical excitatory neurons, D. McSweeney, R. Gabriel, K. Jin, Z. P. Pang, B. Aronow and C. Pak, iScience, October 2022
Additionally, MaxWell Biosystems recently published an application note in collaboration with bit.bio and Charles River Laboratories (CRL) on Developing next-generation in vitro phenotypic assays for Huntington’s disease by combining a precision reprogrammed hiPSC-derived disease model with high-density microelectrode arrays. In this study, CRL functionally characterised human iPSC derived ioGlutamatergic Neurons and the Huntington’s model equivalent, ioGlutamatergic Neurons HTT 50CAG/WTTM from bit.bio using the MaxTwo Multi-Well HD-MEA system. This application note showcases how with the MaxTwo HD-MEA system and MaxLab Live Software Assays, CRL was able to generate phenotypic data demonstrating that bit.bio’s Huntington’s disease model has delayed neuronal network formation, decreased axonal branching, and decreased spontaneous activity compared to the isogenic control.
Here we are highlighting three additional publications illustrating the potential of iPSC as a tool for disease cell modelling from cellular level to a clinical approach:
- Human stem cell models of neurodegeneration: From basic science of amyotrophic lateral sclerosis to clinical translation.
by E. Giacomelli, B. F. Vahsen, E. L. Calder, Y. Xu, J. Scaber, E. Gray, R. Dafinca, K. Talbot, L. Studer, Cell Stem Cell. 29. January 2022.
A thorough recent review of hiPSC models of ALS. Read the paper
- Human iPSC-Derived Neural Models for Studying Alzheimer’s Disease: from Neural Stem Cells to Cerebral Organoids.
by M. Barak, V. Fedorova, V. Pospisilova, J. Raska, S. Vochyanova, J. Sdmik, H. Hribkova, H. Klimova, T. Vanova and D. Bohaciakova, Stem Cell Reviews and Reports, February 2022
A review on differentiation strategies of iPSCs and their utilization in modeling Alzheimer’s disease and potential drug discovery. Read the paper
- Maiden voyage: induced pluripotent stem cell-based drug screening for amyotrophic lateral sclerosis.
by D. Ito, S. Morimoto, S. Takahashi, K. Okada, J. Nakahara, and H. Okano, Brain, January 2023
Clinical study on identification of drug candidates for amyotrophic lateral sclerosis by a high-throughput screening using induced pluripotent stem cells-derived motor neurons. Read the paper