ALS Mouse Study Finds Favor in Muse Stem Cells

ALS Mouse Study Finds Favor in Muse Stem Cells
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Injecting a specific type of stem cells into the bloodstream was able to reduce muscle shrinkage and promote motor neuron survival in a mouse model of amyotrophic lateral sclerosis (ALS), a study found.

According to investigators, the findings indicate these stem cells, known as multi-lineage differentiating stress enduring (Muse) cells, may be a promising treatment option for ALS patients.

The results were reported in the study, “Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis,” published in the journal Scientific Reports.

ALS is a progressive neurodegenerative disorder caused by the gradual loss of motor neurons — nerve cells responsible for controlling voluntary movements — in the spinal cord and brain, leading to muscle weakness and shrinkage (atrophy), and ultimately paralysis.

Although some therapies have been found to successfully slow ALS progression, their therapeutic benefits “are still greatly limited, which demands a novel therapeutic strategy for ALS.”

Originally discovered in 2010, Muse cells are a type of stem cells naturally found in different parts of the body, such as the bone marrow, blood, and connective tissues (tissues that support internal organs and hold other tissues together).

Unlike other types of stem cells, Muse cells have the unique ability to recognize and migrate to injured tissues when injected into the bloodstream, because they contain protein receptors that can pick up signals left by damaged or dying cells. Once they arrive at an injury site, these cells also have the ability to differentiate into the specific cell type that was either damaged or destroyed, promoting tissue repair.

Another important feature is that Muse cells from unmatched donors are not seen as threats by the immune system, and survive in the host for more than six months without the need for immunosuppressive treatments.

Due to their unique abilities, Muse cells have been tested in multiple clinical trials as potential treatments for stroke, spinal cord injury, and myocardial infarction (heart attack).

To investigate if Muse cells also could be a valuable treatment option for ALS, researchers in Japan performed a series of experiments in which they administered these cells to G93A mice, a well-established ALS mouse model with mutations in the SOD1 gene.

To determine the best route of administration for these cells, either directly into the bloodstream or into the animals’ spinal canals, researchers carried out an experiment using both methods to administer green fluorescent Muse cells to animals.

Seven days later, they looked at the animals’ spinal cords to see if they could spot the green fluorescent cells they had injected earlier. They found that the number of fluorescent cells in the spinal cord was much higher after an intravenous (into-the-vein) infusion, supporting this as the best route for administration.

Notably, when injected into the bloodstream, Muse cells not only migrated into the animals’ spinal cords, they also differentiated and gave rise to astrocytes, which are star-shaped cells known to support and protect neurons.

Compared with mice injected with a vehicle (control) solution, or with another type of stem cells called mesenchymal stem cells, those that received Muse cells showed no significant differences in survival or body weight.

But Muse-treated animals showed fewer signs of muscle shrinkage atrophy in their hindlimbs, and significant improvements in muscle strength, compared to the other two groups.

A closer look at their spinal cords showed these animals also had a higher number of viable motor neurons in their spinal cord and more connections between these motor neurons and muscle cells.

The findings suggested that Muse cells promoted motor neuron survival, possibly due to their ability to give rise to astrocytes.

“These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients,” the researchers wrote.

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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