The advantages of stem cell exosomes over stem cells

Extracellular vesicles (EVs) are subcellular entities produced by any cell type. They are
produced spontaneously or in response to stimulation and have a role in intercellular
communication through the transfer of biological material (lipids, proteins, RNAs, etc.). [1]

The characterization of EVs has shown that, like the cells from which they originate,
EVs present and transport specific bioactive molecules. These reflect the phenotype of the
parent cell and result in the vesicles having certain functions. [2] For example, the ability to
interact with the immune system, or to regenerate tissues has been observed in
mesenchymal stem cell (MSCs) EVs [3], cells that originally displayed interesting regenerative
and immunomodulatory properties in many tissue pathologies.

However, given the difficulty of producing these extracellular vesicles, one can
legitimately question the advantages of using stem cell exosomes over stem cells.
To begin with, there is a risk that the stem cells injected into patients will
differentiate or proliferate in an uncontrolled manner. This could lead to tumor in the
patient. This is a serious side effect that does not exist with the use of EVs, as the latter
cannot proliferate. [4]

The use of stem cells can also induce an immunogenic reaction. This risk is greatly
reduced with EVs which are less immunogenic. [5] This has the advantage that the drugs can
be standardized and the risk of an immune reaction from the patients is reduced. [5]
The difference in size observed between stem cells and EVs also plays in favour of
EVs. Stem cells are about 10 um in size. Given their size, they present a risk of vascular
occlusion. EVs, on the other hand, are between 30 nm and 5 um in size depending on their
category (exosomes, microvesicles, apoptotic bodies) and therefore on their biogenesis,
content and function. That eliminates any risk of obstruction.

EVs also have properties that stem cells do not. For example, they have the ability to
cross the selective blood-brain barrier [6], which is an interesting opportunity for research
into treatments for numerous neurodegenerative diseases like AD.
Finally, EVs have the advantage of being preserved fairly easily, by cryopreservation
or lyophilization for example. They can be preserved over the long term and are easier to
transport and store than stem cells [4], which ensures long-term security for the availability
of treatments.

The use of EVs is therefore an alternative to cell-based therapies that reduces many
of the risks associated with these therapies and has many advantages and similar
therapeutic efficacy. Their industrialization and research on the subject are therefore major
challenges in the years to come.

Bibliography :
[1]. Paolicelli, R. C., Bergamini, G. & Rajendran, L. Cellto-cell Communication by Extracellular Vesicles:
Focus on Microglia. Neuroscience 405, 148–157 (2019).

[2]. Yáñez-Mó, M. et al. Biological properties of extracellular vesicles and their physiological
functions. Journal of Extracellular Vesicles 4, 27066 (2015).
[3]. Mancuso, P., Raman, S., Glynn, A., Barry, F. & Murphy, J. M. Mesenchymal Stem Cell Therapy for
Osteoarthritis: The Critical Role of the Cell Secretome. Front. Bioeng. Biotechnol. 7, 9 (2019).
[4]. Mardpour, S. et al. Interaction between mesenchymal stromal cell‐derived extracellular vesicles
and immune cells by distinct protein content. J Cell Physiol 234, 8249–8258 (2019).
[5]. Leavitt, R. J., Limoli, C. L. & Baulch, J. E. miRNAbased therapeutic potential of stem cell-derived
extracellular vesicles: a safe cell-free treatment to ameliorate radiation-induced brain injury.
International Journal of Radiation Biology 95, 427– 435 (2019).
[6]. Saint-Pol, J., Gosselet, F., Duban-Deweer, S., Pottiez, G. & Karamanos, Y. Targeting and Crossing
the Blood-Brain Barrier with Extracellular Vesicles. Cells 9, 851 (2020). 2

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