Promising Opportunities for Treating Neurodegenerative Diseases with Mesenchymal Stem Cell-Derived Exosomes

Biomolecules, 2020 · DOI: 10.3390/biom10091320 · Published: September 15, 2020

Regenerative Medicine Neurology Genetics

Simple Explanation

Neurodegenerative diseases lead to a decline in brain function. Mesenchymal stem cells (MSCs) show promise in aiding brain recovery. MSCs' therapeutic effects are believed to be due to their secretions, especially exosomes. MSC-derived exosomes share characteristics with MSCs, like modulating the immune system and repairing tissue. Introducing foreign cells into the body can cause concerns like immune reactions. MSCs are often cleared quickly after transplantation. The therapeutic benefit seems to be mediated by the MSC-secretome, particularly exosomes. This review discusses advancements in MSC-derived exosome therapies for neurodegenerative disease models, such as Alzheimer’s, multiple sclerosis, and stroke. It examines clinical outcomes and mechanisms of action. The review also addresses limitations and potential improvements for clinical trials.

Study Duration

Not specified

Participants

Animal models

Evidence Level

Review

Key Findings

1
MSC-derived exosomes have shown therapeutic promise in various neurodegenerative disease models, leading to improvement in functional outcomes in stroke, MS, and SCI.
2
In models of stroke, TBI, perinatal brain injury, and SCI, exosome treatment reduced cell death. Exosome therapy contributed to neuronal preservation and neuroprotective and regenerative effects on neurons and synapses.
3
Exosomes can restore cognition impairment and rescue synaptic transmission in mouse models for AD. In stroke models, MSC-derived exosomes enhanced recovery of fine motor function and improved spatial learning and memory.

Research Summary

MSC-derived exosomes can specifically target and accumulate in brain lesion sites in various murine models of diseases, where they improve the behavioral phenotype as well as reducing the inflammatory response. The exosomes orchestrate a series of events that enable recovery and regeneration in neurodegenerative diseases. This improvement is not inferior to that obtained following the transplantation of the parent cells and has the advantage of avoiding adverse events associated with whole cell transplants. Combining the intrinsic properties of exosomes with a targeted medication is suggested as a novel therapeutic approach that might have a dramatic impact on the future of neurodegenerative disease therapy.

Practical Implications

Targeted Drug Delivery

Exosomes can be used as a delivery system for drugs directly to the lesion site, which is especially important for neurodegenerative diseases where reaching the brain is difficult.

Enhanced Therapeutic Efficacy

Loading exosomes with specific molecular agents, such as miRNA, can enhance their functionality and improve outcomes in animal models of neurodegenerative diseases.

Clinical Trial Potential

The use of MSC-derived exosomes in clinical trials, particularly for acute ischemic stroke, shows promise for future studies on patients with various neurodegenerative diseases.

Study Limitations

1
The half-life of exosomes in vivo is estimated to be minutes, and most exosomes have been shown to evacuate within a few hours.
2
There is the possibility that the contents of the exosomes mediate activation of a cascade whose eﬀect is maintained over time. Nevertheless, this possibility cannot be simply assumed, and the question of whether exosome treatment is likely to have a long-lasting eﬀect requires further investigation.
3
Recovery is usually incomplete. Therefore, there is a great value in research designed to further improve MSC-derived exosome treatment.

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