Towards Exosome Therapy for Neurodegenerative Conditions

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Many approaches to stem cell therapy might be replaced in the years ahead by delivery of exosomes secreted by those stem cells. Most cell therapies produce benefits via the signals generated by the transplanted cells. Those signals produce beneficial changes in the behavior of native cells, such as suppression of inflammation or greater tissue maintenance activities. Without extensive engineering of supporting structures the transplanted cells survive only for a short time. Thus why not just deliver the signals? A sizable fraction of cell signaling is delivered via extracellular vesicles such as exosomes, membrane-wrapped packages of signal molecules that pass between cells. Harvesting exosomes from cell cultures for use in therapy is logistically easier than building cell therapies, and thus a great many research groups and companies are presently working on regenerative therapies based on delivery of natural or modified exosomes.

Despite the recent advances in the biology of neurodegenerative diseases, these disorders remains incurable, and most of the existing drugs provide only symptomatic relief and do not affect the progression of the disease. For this reason, there is a pressing need to identify alternative therapies to treat these disorders. Therefore, there is an urgent need for new treatments for these diseases, since the World Health Organization has predicted that neurodegenerative diseases affecting motor function will become the second-most prevalent cause of death in the next 20 years.

In this sense, cell therapy, using stem cells, has been recognized as the best candidate for treating incurable diseases, including neurodegenerative disorders. However, in the last decade, accumulating evidence supports the idea that mesenchymal stem cells (MSCs) perform their therapeutic roles in a paracrine manner. For a long time, it was considered that the therapeutic effects of the stem cells were associated with the replacement of dead cells. However, in a model of kidney injury it was verified that transplanted stem cells remain in the injury site up to a few days only, and, subsequently, are not found in the tissue. Similar results were observed in subsequent studies.

Altogether, these data suggest that the therapeutic effects of MSCs are mediated by their "secretome", which is composed of a spectrum of protective bioactive molecules, which are comprised of anti-inflammatory cytokines, growth factors, neuronal factors, and antioxidants. The rediscovery that cells secrete a plethora of factors into nanosized vesicles surrounded by a lipid bilayer membrane (extracellular vesicles) has allowed exploring the therapeutic use of these vesicles in a novel therapeutic modality known as cell-free therapy.

The class of extracellular vesicle known as exosomes emerge as a promising therapeutic approach for neurodegenerative diseases. This is because, due to their nano-sized diameter, the exosomes can cross the blood brain-barrier, acting as carriers of bioactive molecules naturally secreted by their derived cells, or they can be engineered as carriers of drugs. Despite the evidence of the benefits of cell-free therapy for neurodegenerative diseases, efforts are necessary to improve the available exosome isolation methodologies in order to realize scalable vesicles production for clinical purposes. In addition, it is also crucial to provide guidelines for studying these vesicles in order to guarantee acceptance criteria by regulatory agencies.

Link: https://doi.org/10.3390/cells9122663

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source https://www.fightaging.org/archives/2020/12/towards-exosome-therapy-for-neurodegenerative-conditions/