One of the most notorious effects of the increase in life expectancy is its impact on the brain. The extra years that we have gained (more than 35 since 1920) bring new experiences, greater knowledge, but also consequences for mental health and brain activity. To try to solve this, a team from the University of Copenhagen, has transplanted specialized cells into the brains of mice and discovered that they not only compete and replaced diseased cells, but also to the aged. The findings open the door to the development of an effective treatment for a variety of conditions such as multiple sclerosis, ALS, Alzheimer’s disease, autism and schizophrenia.
We go through steps to understand the importance of the finding. Glial cells is a general term for cells that are a support system for nerve cells, or neurons. Progenitor cells, for their part, are descendants of stem cells that can differentiate into specific cell types and, in the case of glial cells, human glial progenitor cells (hGPCs) differentiate into subtypes, including astrocytes and oligodendrocytes.
Astrocytes comprise the majority of cells in our central nervous system, providing support and protection for neurons, transporting nutrients, and removing waste. Meanwhile, oligodendrocytes deposit and maintain the lipid-rich insulating sheath called myelin around some axons, the part of a neuron that connects with another neuron and allows the transmission of nerve impulses and is markedly reduced in diseases such as Alzheimer’s. In general, dysfunctional astrocytes and oligodendrocytes have been associated with various neurodegenerative and neuropsychiatric conditions.
Those responsible for the study, published in Nature, had already shown that healthy human glial cells were capable of replacing diseased mouse glial cells when transplanted into mouse models with Huntington’s disease. But now they wanted to go a step further and see if human cells could replace cells that were also human and not mouse cells. To do this, they introduced healthy cells into ‘chimeric’ mice injected with human-derived stem cells with Huntington’s disease. The results showed that the healthy cells outnumbered and completely replaced the diseased ones.
“We transplanted the healthy human cells into the mice that were ‘humanized’ with the Huntington-expressing mutant glia, and the healthy glial cells overcame and replaced diseased gliacausing them to disappear,” says Steven Goldman, leader of the study.
Interestingly, the researchers found that when hGPCs from younger donors were introduced into the brains of humanized mice, they competed with healthy cells, not sick but aged, and replaced them too. The researchers say their findings that healthy hGPCs replaced both diseased and aged cells are significant, highlighting the potential for developing treatments that could be used in a wide range of scenarios.
“The findings show that it wasn’t just a matter of healthy cells outperforming diseased ones, but this was much broader in terms of its potential use, because we could get into all kinds of disease targets where we have older or diseased glial populations – adds Goldman -. The upside is significant in terms of where this could go because there are all kinds of glial cell diseases.”
Glial cells are critical for the development of certain neuropathologies. The neurodegenerative conditions amyotrophic lateral sclerosis (ALS), epilepsy, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease, have been associated with dysfunctional glial cells. Like neuropsychiatric disordersautism spectrum disorder (ASD), bipolar disorder and schizophrenia.
“If we can replace diseased and aged cells, then we should be able to restore aspects of normal function in these degenerative diseases, as we have seen with our experimental models of Huntington’s disease,” Goldman concludes. But that’s basically a proof of principle because we think the same thing would also work in some of these other diseases, like lateral sclerosis, some of the frontotemporal dementias, and even some of the hereditary schizophrenias, as well as myelin diseases and age-related white matter loss. We hope to have the next results in a year and a half to start human trials, something that would happen in two years“.
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