Extracellular Vesicles from Mesenchymal Stem Cells: Towards Novel Therapeutic Strategies for Neurodegenerative Diseases

Neurodegenerative diseases are fatal disorders of the central nervous system (CNS) which currently lack effective treatments. The application of mesenchymal stem cells (MSCs) represents a new promising approach for treating these incurable disorders. Growing evidence suggest that the therapeutic effects of MSCs are due to the secretion of neurotrophic molecules through extracellular vesicles. The extracellular vesicles produced by MSCs (MSC-EVs) have valuable innate properties deriving from parental cells and could be exploited as cell-free treatments for many neurological diseases. In particular, thanks to their small size, they are able to overcome biological barriers and reach lesion sites inside the CNS. They have a considerable pharmacokinetic and safety profile, avoiding the critical issues related to the fate of cells following transplantation. This review discusses the therapeutic potential of MSC-EVs in the treatment of neurodegenerative diseases, focusing on the strategies to further enhance their beneficial effects such as tracking methods, bioengineering applications, with particular attention to intranasal delivery as a feasible strategy to deliver MSC-EVs directly to the CNS in an effective and minimally invasive way. Current progresses and limiting issues to the extent of the use of MSC-EVs treatment for human neurodegenerative diseases will be also revised.

Automated summary

Neurodegenerative diseases, currently lacking effective treatments, can potentially be treated using mesenchymal stem cells (MSCs). These cells secrete neurotrophic molecules through extracellular vesicles (EVs) which have therapeutic potential due to their innate properties and ability to reach the central nervous system. This review explores the use of MSC-EVs in treating neurodegenerative diseases, discussing strategies to enhance their effects and highlighting intranasal delivery as a minimally invasive option. The current progress and limitations of MSC-EV treatment for human neurodegenerative diseases are also reviewed.