Oligodendrocyte progenitor cells are neural cells which give rise to oligodendrocytes – glial cells in the central nervous system. While most oligodendrocyte progenitor cells differentiate into oligodendrocytes during the development of the central nervous system at a young age, some remain as progenitor cells until adulthood.
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Oligodendrocytes and their progenitors
Oligodendrocytes are involved in the myelination of the axons, which in turn improves the function of the nerves and offers trophic support to longer axons. When oligodendrocytes are lost, neurons themselves and neural transmission are also lost. This occurs in certain diseases, such as multiple sclerosis.
The characteristics of oligodendrocytes and their progenitors are remarkably different. Mature oligodendrocytes are fragile, fibrous, fixed in place, and do not replicate. Progenitor cells, on the other hand, are highly mobile, replicate at high rates, and are mechanically sturdy. The higher flexibility shown by the progenitor cells has made them an attractive target in pursuit of the cure for demyelination diseases.
The production of oligodendrocyte progenitor cells
Oligodendrocyte progenitor cells are derived from stem cells. During development, production starts in the spinal cord where sonic hedgehog (SHH) signaling molecule controls transcription of appropriate genes for progenitor cell production.
Production occurs in three distinct waves, where the first wave occurs at embryonic day 12.5, the second at embryonic day 15.5 controlled by fibroblast growth factor (FGF) and reduced bone morphogenetic protein (BMP), and the third wave occurs at birth.
Production in the forebrain is similar to that of the spinal cord, whereby production occurs in three distinct waves within similar time frames as in the spinal cord. The first wave is controlled by SHH, but the second wave is under the control of glutathione synthetase 2 (Gsh2). The oligodendrocyte progenitor cells migrate throughout the brain to colonize different areas in a largely even distribution.
Once migration is finished, many progenitor cells mature into oligodendrocyte cells while others remain as resident progenitor cells. The production of oligodendrocyte progenitor cells continues in adulthood, where they are generated from neural progenitor cells. Oligodendrocyte progenitor cells can also be artificially produced from induced pluripotent stem cells.
Roughly 3% of cells in the human brain in adults are oligodendrocyte progenitor cells, which can become mature oligodendrocytes to assist in maintaining myelin turnover. While the oligodendrocyte progenitor cells normally give rise to oligodendrocytes, or sometimes astrocytes, they have been shown to be able to mature into functional neurons of varying phenotypes.
Function and uses
Oligodendrocyte progenitor cells’ natural function is to maintain the population of oligodendrocyte cells and, therefore, keep the brain in good health. The differentiation of progenitor cells into oligodendrocytes in the mature brains is triggered by the injury to the central nervous system.
It has been indicated that the progenitor cells could be useful in treating neuronal diseases, particularly demyelinating diseases. However, difficulty in obtaining large quantities of the required progenitor cells has hampered this type of research.
Experiments on mice have indicated that oligodendrocyte progenitor cells derived from induced pluripotent stem cells have the capacity to mature into oligodendrocytes and astrocytes, gaining myelinating function. However, when co-cultured with neurons derived from induced stem cells and from embryos, mature myelination formation was not unambiguous. Furthermore, the nodes of Ranvier necessary for proper conductivity of the neuron need to be established to confirm that the myelination is healthy.
What is the role of oligodendrocyte progenitor cells in multiple sclerosis?
Diseases such as multiple sclerosis (MS) involve an impaired ability to generate oligodendrocyte cells to make up for losses. This eventually leads to demyelination and subsequent loss of function of neurons. Remyelination occurs spontaneously in MS as a result of triggering oligodendrocyte progenitor cells to mature; however, this decreases with age and disease progression.
The decrease is largely due to immune responses that lead to reaction cascades which ultimately impair the ability of oligodendrocytes and their progenitor cells to remyelinate axons. It is hoped that an increased understanding in how progenitor cells are being targeted and how they react can lead to more effective treatment options to slow, or even completely halt the progression of MS.
Sources
- Goldman S.A. and Kuyper N.J. (2015). How to make an oligodendrocyte. Development. https://doi.org/10.1242/dev.126409
- Dulamea A.O. (2017). The contribution of oligodendrocytes and oligodendrocyte progenitor cells to central nervous system repair in multiple sclerosis: perspectives for remyelination therapeutic strategies. Neural Regeneration Research. https://doi.org/10.4103/1673-5374.221146
- Yamashita T., et al. (2017). Differentiation of oligodendrocyte progenitor cells from dissociated monolayer and feeder-free cultured pluripotent stem cells. PLoS ONE. https://doi.org/10.1371/journal.pone.0171947
Further Reading
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