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Effects of Muse Cell on a Mouse Model With Acute Encephalopathy
Tatsuya Kawaguchi1,2,3, Tetsuji Mori2, Kaori Adachi4
1Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Introduction:
Acute encephalopathy (AE) in childhood due to a viral infection causes convulsions and altered consciousness, leading to severe sequelae and death. Among the four types of AE, cytokine storm-induced AE is the most severe and causes serious damage to the brain. Moreover, a fundamental treatment for AE has not been established yet. Recently, it has been shown that the administration of multilineage-differentiating stress-enduring (Muse) cells, a population of mesenchymal stem cells, improves symptoms in various types of brain injuries when administered in the subacute phase (1-7 days after brain damage). We aimed to examine the effects of Muse cells in a cytokine storm-induced AE animal model using immunocompromised nonobese diabetic/severe combined immunodeficiency (NOD/SCID) neonatal mice.
Methods:
We established a modified protocol to induce AE-like symptoms in NOD/SCID. Then, Muse cells were injected at an acute phase (2-4 h after hyperthermia treatment).
Results:
Injection of Muse cells significantly improved body weight gain 1 day after treatment and the survival ratio for 3 weeks.
Conclusion:
These effects could be a result of the direct and/or indirect upregulation of IL-10, an anti-inflammatory cytokine, in the Muse cell-treated brain. Although non-Muse cells, a residual cell population in the bone marrow after isolating Muse cells, also improved some symptoms, their effects were weaker than those of Muse cells. Our results indicate that the injection of Muse cells in the acute phase has an effect on AE, suggesting that they exert their therapeutic effects not only in the subacute phase but also in the acute phase.
Insights
Multilineage-differentiating stress-enduring (Muse) cells show promise in treating acute encephalopathy (AE) in a neonatal mouse model. Muse cell injection in the acute phase improved survival and body weight, suggesting early therapeutic potential.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Immunology
Background:
- Acute encephalopathy (AE) in children, often viral, causes severe brain damage, seizures, and death.
- Cytokine storm-induced AE is particularly severe, with no established fundamental treatment.
- Multilineage-differentiating stress-enduring (Muse) cells, a type of mesenchymal stem cell, show potential in treating brain injuries during the subacute phase.
Purpose of the Study:
- To investigate the therapeutic effects of Muse cells in an acute phase cytokine storm-induced AE model.
- To evaluate Muse cell efficacy in immunocompromised nonobese diabetic/severe combined immunodeficiency (NOD/SCID) neonatal mice.
Main Methods:
- A modified protocol was used to induce AE-like symptoms in NOD/SCID mice.
- Muse cells were administered during the acute phase (2-4 hours post-hyperthermia treatment).
Main Results:
- Muse cell injection significantly improved body weight gain within 1 day post-treatment.
- A notable increase in the survival ratio was observed over a 3-week period in Muse cell-treated mice.
Conclusions:
- Muse cells demonstrate therapeutic potential in the acute phase of AE, not just the subacute phase.
- The observed benefits may be linked to the upregulation of the anti-inflammatory cytokine IL-10.
- While non-Muse cells showed some effect, Muse cells exhibited superior therapeutic efficacy.
