What is it about?
It would be clinically ideal to target astrocytes in vivo for conversion into oligodendrocyte lineage cells to reduce astrogliosis and generate new myelinating cells. Here, we prepared a GFP-labeled human astrocyte cell line, treated with epigenetic modifiers trichostatin A or 5-azacytidine and transplanted them into cuprizone-induced demyelinated mice brains. The fate of the transplanted astrocytes was studied at days 7, 14 and 28 post-transplantation. GFP+ astrocytes were reduced over time, whereas the GFP+ oligodendrocyte lineage cells were found on days 14 and 28. Nontreated astrocytes did not convert to myelinating cells following transplantation. Cell conversion was proved in vitro by maintaining the treated cells in oligodendrocyte progenitor cell medium. These findings seem promising for the application of epigenetic modifiers, especially their targeted delivery to glial scars to treat demyelinating diseases.
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Why is it important?
In diseases like MS with the loss of myelinating cells, providing new oligodendrocytes will help with the myelin repair process. On the other hand, reactive astrocytes within the lesion areas or demyelinated plaques inhibit remyelination and axonal regeneration. The results of this study showed that using chemicals, astrocytes could be converted to myelinating cells. Such an approach removes the repair inhibitory cells and generates prorepair cells at the same time.
Perspectives
Since chemicals cannot discriminate between the cells, developing targeted methods for delivery of chemicals to the lesion area is required for future study, especially for chemicals that possess notable side effects. As we are attempting, research laboratories may also try to provide a list of chemicals which can convert astrocytes to OPCs or even neurons. This strategy may also work for other neural disorders, such as spinal cord injury, that are accompanied with demyelination and demyelination-induced axonal degeneration in some extents of their pathology. While reprogramming approaches are mostly based on transcription factors delivery by viral particles, cell conversion using chemicals have several safety advantages. Such an approach for making new neurons by in vivo delivery of chemicals may also contribute to a wide range of neurodegenerative diseases. A defined pathway of the conversion may be uncovered by future experiments to provide a deep understanding of the involved mechanisms that promise for optimizing the procedure for better OPC quality and the improved efficacy of cell conversion.
Mohammad Javan
Tarbiat Modares University
Read the Original
This page is a summary of: In vivo conversion of astrocytes to oligodendrocyte lineage cells using chemicals: targeting gliosis for myelin repair, Regenerative Medicine, October 2018, Future Medicine,
DOI: 10.2217/rme-2017-0155.
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