2023-07-18 16:39:04
Replacing damaged or aged cells with healthy ones is one approach to treat some neurological and psychiatric diseases -such as Huntington’s, amyotrophic lateral sclerosis (ELA) and schizophrenia-. Now a new study published in the journal «Nature Biotechnology» answers important questions about the feasibility of treatments that aim to replace diseased and aging cells in the central nervous system with healthy ones. His findings have implications for a series of neurological and psychiatric disorders that have been linked to glia, a population of cells that promote brain health and function.
“A wide variety of disorders that we associate with neuronal loss now appear to be caused by dysfunctional glial cells,” says Professor of Neurology from the University of Rochester Medical Center (URMC)Steve Goldman, lead author of the new study. “This makes these diseases attractive targets for stem and progenitor cell-based therapies.”
The work describes the capacity of human glial progenitor cells – precursor cells that can give rise to both astrocytes like oligodendrocytess, the two main types of glia- to compete with each other in the adult brain, and the competitive advantage of young and healthy cells over aged and diseased ones.
A number of important recent advances are behind the new findings. In 2013, Goldman and his colleagues first reported strategies for producing the glial supporting cells of the brain from embryonic stem cells.
In further research, the lab transplanted these cells into the brains of baby mice, creating human glial-chimeric mice, a technical breakthrough that allows researchers to study human glial cells in the living brain. The team showed that, after transplantation, cells human glial progenitors rapidly outperformed native cellsgiving rise to brains with mouse neurons and human glia.
In subsequent experiments, the lab transplanted human glial cells with the mutation of the Huntington’s disease (HTT). They found that this mutation affected glial progenitor cell function, resulting in poor production of astrocytes and oligodendrocytes. The lab also demonstrated that transplantation of healthy human glial progenitor cells into mouse models of Huntington’s slowed the progression of the disease, reinforcing the important role that glial dysfunction plays in this still intractable neurodegenerative disease.
As these previous studies were limited to the transplantation of human cells into the brain of mice, the question remained as to whether if human cells transplanted into another human brain would produce the same kind of profit.
Highlights the potential value of cell replacement therapies by demonstrating that healthy human glia will outcompete and replace diseased human cells
The new study of «Nature Biotechnology» strongly suggests that the answer to this question is yes, and highlights the potential value of cell replacement therapies by demonstrating that healthy human glia will surpass and replace to diseased human cells.
To demonstrate this, the researchers first implanted human glial progenitor cells with the HTT mutation into the brains of newborn mice. Once the animals reached adulthood, the researchers transplanted healthy human glial cells, which crowded out and killed their Huntington’s disease counterparts.
“In the striatum, our target area, the healthy cells pushed out the diseased cells and eventually completely replaced the glial progenitor population,” explains Goldman. “You can see a wave of migration and a border in which cells expressing the HTT mutation They die and are replaced by healthy cells.
In a complementary set of experiments, the researchers found that younger healthy human glial progenitors outcompeted older and otherwise healthy human glia, suggesting that cell youth is a critical determinant of competitive success.
“These findings have important therapeutic implications. since they suggest that in the adult human brain, the resident glia – diseased or simply aged – can be replaced after the introduction of younger and healthy cells”, affirms Goldman.
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