Commonly unknown, oligodendrocytes are the cells in which the process of myelination occurs within the central nervous system. They are perhaps one of the most vulnerable cells within our bodies; their extensive cell lineage, or growth, requires multiple processes, including proliferation, differentiation, migration, all which have to properly happen at the correct times (or else the cells won’t form correctly), finally resulting in myelination, to form the outer sheath of the cell.
They “hang” onto, first, the axons of the brain, which connect to our synapses (which send signals to other neurons to eventually reach our brain), and second, our unmyelinated cells, the nodes of Ranvier, which allow faster action potentials in neurons. Action cells assist in the propagation of faster signals within our brain. But why are oligodendrocytes important?
Oligodendrocytes are crucial to myelinating axons. The dysfunction of oligodendrocytes is what contributes to multiple sclerosis, commonly known as a demyelinating disorder. This following study, using animal models and cadavers, demonstrates why exactly it’s so difficult to study multiple sclerosis in human models.
Since post-mortum humans and animals cannot develop multiple sclerosis, researchers at Johns Hopkins’s Lieber Institute for Brain Development used hiPSCs, human induced pluripotent stem cells, to stimulate multiple sclerosis in these models. They mimic, or replace, the role of oligodendrocytes in regular, human models. Fascinatingly, some of these hiPSCs can be taken from certain M.S. patients themselves, creating a patient-specific approach to creating multiple sclerosis. These created models can also help study the early stages of M.S., which are often missed in human patients. To further add, and possibly the most important note, we can better understand the cellular and molecular pathways associated with multiple sclerosis, like inflammatory or oligodendrocyte-dysfunctional pathways.
In M.S., demyelinated lesions cause inflammation, which damages neurons. Remyelination, if not done properly, can expose the axons of the brain to immune attacks, creating the potential for a common cold to be debilitating. hiPSCs show potential of neural lineage, but are different with progressive M.S. (relapsing, etc.). According to the hiPSCs conducted by the researchers in this article, inflammatory tests reveal that sensitivity affects cell development, and abnormal cell migration could contribute to multiple sclerosis; a further example to how hiPSCs proffer insight for studying M.S. and treating it.
To summarize, understanding re/demyelination is extremely important to create an effective therapy. Patient-derived hiPSCs can help with genetic challenges (as genetics do play a role in M.S.), and, like aforementioned, can help create a more personal therapeutic intervention for patients.
Citations
Shim, Gina, et al. “Utilizing hipsc-derived oligodendrocytes to study myelin pathophysiology in neuropsychiatric and neurodegenerative disorders.” Frontiers in Cellular Neuroscience, vol. 17, 2024, https://doi.org/10.3389/fncel.2023.1322813.
Comments