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Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury
Karla Drommelschmidt1, Meray Serdar1, Ivo Bendix1
1Department of Paediatrics I/Neonatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Insights
Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) show promise for treating preterm brain injury. MSC-EV treatment reduced inflammation, improved white matter microstructure, and enhanced long-term cognitive and motor functions in a rodent model.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Developmental Biology
Background:
- Preterm brain injury, a significant cause of lifelong disability, results from multifactorial processes including inflammation-induced white and grey matter damage.
- Current treatments for preterm brain injury are limited, highlighting the need for novel therapeutic strategies.
- Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) have demonstrated therapeutic potential in regenerative medicine.
Purpose of the Study:
- To investigate the therapeutic effects of MSC-EV treatment on brain microstructure, maturation, and inflammatory processes in a rodent model of preterm brain injury.
- To evaluate the long-term functional outcomes following MSC-EV administration in this model.
Main Methods:
- Wistar rats at postnatal day 3 (P3) received intraperitoneal injections of lipopolysaccharide (LPS) or saline, followed by two doses of MSC-EVs.
- Cellular degeneration, reactive gliosis, and myelination were assessed using immunohistochemistry and Western blot.
- Long-term cognitive and motor functions were evaluated through behavioral testing, and white matter microstructure was analyzed using diffusion tensor imaging at P125.
Main Results:
- MSC-EV treatment significantly reduced LPS-induced neuronal degeneration, microgliosis, and astrogliosis.
- MSC-EVs restored short-term myelination deficits and long-term white matter microstructural abnormalities.
- Improved long-lasting cognitive functions were observed in MSC-EV treated rats.
Conclusions:
- MSC-EVs effectively ameliorate inflammation-induced cellular damage in a rat model of preterm brain injury.
- MSC-EVs represent a potential novel therapeutic option for preventing neuronal cell death, restoring white matter integrity, reducing gliosis, and improving long-term functional outcomes.
- Further research into MSC-EVs could lead to effective treatments for preterm brain injury and its associated disabilities.
Objective:
Preterm brain injury is a major cause of disability in later life, and may result in motor, cognitive and behavioural impairment for which no treatment is currently available. The aetiology is considered as multifactorial, and one underlying key player is inflammation leading to white and grey matter injury. Extracellular vesicles secreted by mesenchymal stem/stromal cells (MSC-EVs) have shown therapeutic potential in regenerative medicine. Here, we investigated the effects of MSC-EV treatment on brain microstructure and maturation, inflammatory processes and long-time outcome in a rodent model of inflammation-induced brain injury.
Methods:
3-Day-old Wistar rats (P3) were intraperitoneally injected with 0.25mg/kg lipopolysaccharide or saline and treated with two repetitive doses of 1×108 cell equivalents of MSC-EVs per kg bodyweight. Cellular degeneration and reactive gliosis at P5 and myelination at P11 were evaluated by immunohistochemistry and western blot. Long-term cognitive and motor function was assessed by behavioural testing. Diffusion tensor imaging at P125 evaluated long-term microstructural white matter alterations.
Results:
MSC-EV treatment significantly ameliorated inflammation-induced neuronal cellular degeneration reduced microgliosis and prevented reactive astrogliosis. Short-term myelination deficits and long-term microstructural abnormalities of the white matter were restored by MSC-EV administration. Morphological effects of MSC-EV treatment resulted in improved long-lasting cognitive functions INTERPRETATION: MSC-EVs ameliorate inflammation-induced cellular damage in a rat model of preterm brain injury. MSC-EVs may serve as a novel therapeutic option by prevention of neuronal cell death, restoration of white matter microstructure, reduction of gliosis and long-term functional improvement.
