hiPSC-Derived Neural and Glial Cells for Disease Modelling and Drug Discovery

In recent years, understanding of the central nervous system (CNS) has significantly improved. New products and technologies have enabled the exploration of the molecular mechanisms involved in development, learning, synaptic function, electrical conductivity and memory function.

Advances in knowledge about the onset and deterioration of these systems in the context of neurological disorders such as amyotrophic lateral sclerosis (ALS), epilepsy, Parkinson’s, Alzheimer’s and Huntington’s diseases as well as psychiatric conditions have also been facilitated.

Neural Stem Cells

Neural Stem Cells

Neurons

Neurons

Astrocytes

Astrocytes

Modeling Neural Networks: From Animal Models to Human Cells

Primary findings in the field of neuroscience have been elucidated by animal models. However, due to restricted resources and access, the use of human cells has been limited. New opportunities have been created by the discovery of pluripotent stem cell (iPSC) methodology in 2012, which won a Nobel-prize. Typically, cells derived from these protocols are sourced from peripheral blood mononuclear cells (PBMCs) or fibroblasts.

Reprogramming can then take place either using viral transduction (e.g. Sendai) or footprint-free non-integrating episomal vectors in order to introduce factors SOX2, OCT4, MYC and KLF4, which introduce pluripotency. After that, cells can be differentiated into a number of cell types, including several glial and neural lineages.

Human iPSCs provide a virtually unlimited resource of patient-specific and healthy glial and neural cells for use in toxicological screening, biomedical research and drug evaluation. This has provided researchers with a greater understanding of the characteristics of each cell type during the differentiation process as well as factors that govern the mature cell phenotype.

Furthermore, mature, terminally-differentiated cells give a platform, based on human cells, for the assessment of efficacy of current treatments and identification of novel therapeutic targets for neurological conditions. This increases the possibility of achieving effective regenerative medicine.

Complete Complementary iPSC-Derived Neural Cell Culture Systems

It is important that, in all systems, the in vitro differentiation mimics the in vivo development. This is achievable by culturing cells under fully-defined, xeno-free conditions while expanding stem cells, then differentiating them into high-purity neuronal cell types, and finally maintaining them long-term in vitro.

Researchers can generate pure cell populations for use in disease modeling and drug discovery using human iPSC-derived neural stem cells (NSCs), astrocytes, neurons and culture reagents such as those offered by Axol. Cultures such as this could be used to determine the direct effect of compounds on these specific cells, or elucidate the mechanisms that occur in neuronal development or precede the onset of neurodegenerative conditions. They could also be co-cultured to facilitate more complex analysis of the CNS in vitro.

Using technologies such as CRISPR/Cas9 gene editing may facilitate further precision with the creation of isogenic cell lines with disease-specific mutations. This means that cells can be compared without any confounding genetic or environmental factors that may otherwise be present in samples from different individuals.

Human iPSC-Derived Cell Types in Disease Modeling and Drug Discovery

Human iPSC-Derived Neural Stem Cells

NSCs give rise to cell types that are more advanced, for example oligodendrocytes, astrocytes and neurons that connect to form networks in the spinal cord and brain. These networks control excitatory, modulatory or inhibitory responses in the body by transmitting chemical signals (acetylcholine, dopamine, serotonin, glutamate or gamma aminobutyric acid (GABA) across synaptic junctions.

Human iPSC-Derived Cerebral Cortical Neurons

It is possible to differentiate NSCs into cerebral cortical neurons (CCNs). These play an important role in memory formation and learning and are located in the outer layer of the brain. It follows therefore that Alzheimer’s disease may be caused by degeneration of these neurons.

Human iPSC-Derived Dopaminergic Neurons

Dopaminergic neurons are important for dopamine transmission and network formation. Most of these cells are found in the substantia nigra and ventral tegmental areas of the midbrain. Multiple brain functions as well as a broad range of behavioral processes such as reward, mood, stress and addiction, are controlled by these neurons. Therefore, an imbalance of dopamine levels or decrease in the number of these cells can result in motor dysfunction and deterioration. This can cause conditions such as attention deficit hyperactivity disorder (ADHD), Parkinson’s disease, drug addiction or psychosis.

Human iPSC-Derived Astrocytes

Astrocytes are glial cells that support both the trophic and metabolic development of neurons. As they mature, astrocytes have a range of functions in myelination, neuronal migration and synaptogenesis. These functions are well-established and stage-specific. Dysfunction of astrocytes has been described in conditions such as Alzheimer’s and Alexander’s diseases and fragile X and Rett syndromes. Furthermore, some conditions are associated with region-specific astrocytes, for example ventral-spinal in ALS or midbrain in Parkinson’s disease.

Axol can provide iPSC-Derived Cerebral Cortical Neurons and Neural Stem Cells from patients with Huntington’s and Alzheimer’s disease as well as from controls. The Xeno-Free Neural Cell Culture System from Axol is also available and has been optimized for long-term culture of pure neuronal cell populations.

In addition, Axol provides an iPSC-Derived Dopaminergic Neuron Precursor Kit as well as a variety of derived astrocytes at different developmental stages including an iPSC-Derived Mature Astrocytes Kit and an iPSC-Derived Astrocyte Progenitor Kit. A complete suite of reprogramming, custom cell sourcing, gene-editing and differentiation services for creating isogenic cells lines is also available from Axol.

About AXOL Biosciences

Axol specializes in human cell culture.

Axol produces high quality human cell products and critical reagents such as media and growth supplements. We have a passion for great science, delivering epic support and innovating future products to help our customers advance faster in their research.

Our expertise includes reprogramming cells to iPSCs and then differentiating to various cell types. We supply differentiated cells derived from healthy donors and patients of specific disease backgrounds. As a service, we also take cells provided by customers (primary or iPSC) and then do the reprogramming (when necessary) and differentiation. Clearly, by offloading the burden of generating cells, your time is freed up to focus on the research. Axol holds the necessary licenses that are required to do iPSC work.

The package wouldn't be complete without optimized media, coating solutions and other reagents. Our in-house R&D team works hard to improve on existing media and reagents as well as innovate new products for human cell culture. We also supply a growing range of human primary cells; making Axol your first port of call for your human cell culture needs.


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Last updated: Sep 30, 2019 at 11:04 AM

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