Abstract
This chapter examines the clinical translation of mesenchymal stromal/stem cell–derived extracellular vesicles (MSC–EVs) and related cell-free therapeutic products. It reviews the human evidence landscape, including prospective cohorts, early-phase trials, randomized studies, expanded-access experiences, and emerging applications across respiratory, renal, neurological, inflammatory, pain, wound healing, and fibrotic indications. Particular attention is given to product definition, parental cell source, route of administrationRoute of administration, dose metrics, potency, release testing, safety monitoring, and clinically meaningful endpoints. The available evidence supports feasibility and generally favorable short-term tolerability for several product–route combinations, but it does not establish a therapeutic class effect. Interpretation remains limited by small samples, heterogeneous manufacturing and isolation methods, inconsistent dose units, incomplete potency data, short follow-up, changing standards of care, and limited independent replication. By integrating clinical findings with chemistry, manufacturing, and controls, this chapter provides a product-specific framework for designing future MSC–EV trials and advancing the field from exploratory administration toward reproducible, mechanism-linked, and regulator-ready biologic development.