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Sufficient pre-clinical data have been accumulated to consider how MSC-sEVs might be used clinically for the treatment of SCI. This review discusses: (1) the SCI patient population which may benefit from MSC-sEVs treatments, (2) potential sources of MSCs for production of clinically useful MSC-sEVs, (3) dosaging of MSC-sEVs required for therapeutic efficacy, (4) timing and method of delivery of the sEVs, (5) cell targets of MSC-sEVs and their mechanism of action, (6) possible protocols for producing clinically useful quantities of MSC-sEVs, and (7) the criteria for evaluating an MSC-sEVs treatment product. 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