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MSC beneficial effects and limitations, and MSC-derived extracellular vesicles as a new cell-free therapy for tissue regeneration in irradiated condition
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International audience. The unique immunomodulatory and anti-inflammatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type to contribute to the reparation of tissues and organs affected by high exposure to ionising radiation. Relevant experience has been obtained using MSCs in the medical treatment of overexposed persons from radiation accidents worldwide. Although MSCs have provided substantial clinical evidence of their therapeutic efficacy in local radiation injuries, in combination with other treatments, there are still challenges to overcome regarding authorizations, production, conditions of use and applicability as a medical countermeasure. The success of MSC-based therapy was established based on the premise that transplanted cells home in to and engraft within injured tissues and subsequently differentiate to replace injured cells. However, subsequent work has affirmed that the paracrine effect is mediated by secreted extracellular vesicles, particularly exosomes in several models of injury such as myocardial infarction, kidney injury and skeletal muscle repair. This paracrine hypothesis also suggests that certain safety concerns related to stem cell transplantation, could be readily overcome using stem cell-derived extracellular vesicles in the absence of the stem cells of origin. Advances have already been made towards the translation of MSC-derived extracellular vesicle in regenerative therapy. Moreover, according to preclinical studies, MSC-derived extracellular vesicles may have a promising role in the medical management of radiation injuries. Current and future perspectives on these cell-free therapies applied to treat overexposed persons to ionising radiation are part of this opinion paper.
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