en Cell Biology Cell Biology Editorial Editorial <span style="font-size:12pt"><span style="line-height:200%"><span sans-serif="" style="font-family:Calibri,"><span new="" roman="" style="font-family:" times="">Mesenchymal stromal cell&ndash;derived extracellular vesicles (MSC-EVs) are promising candidates for cell-free therapeutics, but the copy-number mathematics -most EVs contain fewer than one copy of a given microRNA (miRNA)- forces a reconsideration of mechanisms and development strategies. Translation will require disciplined adherence to MISEV2023 standards: definitions of transparent source and separation; absolute quantification of cargo by digital PCR (dPCR) or UMI-aware small RNA sequencing; and validated potency assays (e.g., NF-&kappa;B suppression, macrophage polarization) linked to critical quality attributes (CQAs). Dosing should evolve from particle/protein counts to a triad of particles, protein, and miRNA copies, ideally tied to activity-based units. Clean separations are essential to avoid misattributing effects to vesicles in the presence of non-vesicular RNA. Safety assessment, including TF/CD142 and thrombogenicity, must guide route selection. Manufacturing should standardize CPP-to-CQA control in TFF-based systems, while stability testing must minimize freeze&ndash;thaw cycles and validate lyophilization. The first approvable product will likely use local delivery, a small number of defined miRNAs, and copy-number-anchored dosing. The translational mandate is clear: count molecules, link counts to function, and dose based on biology.</span></span></span></span><br> &nbsp; Mesenchymal stromal cells (MSCs), Extracellular vesicles (EVs), microRNA (miRNA), MSC-EV-microRNAome, MISEV2023 793 796 http://ijmcmed.org/browse.php?a_code=A-10-85-5&slc_lang=en&sid=1 Farshid Yeganeh fyeganeh@gmail.com 100319475328460035441 100319475328460035441 No Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Hadi Parsian hadiparsian@yahoo.com 100319475328460035442 100319475328460035442 Yes Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.