GMP-compliant products-mesenchymal stem cells derived extracellular vesicles: applications, challenges and prospects

Mesenchymal stem cells (MSCs) are extensively employed in cellular therapy owing to their distinctive paracrine function and multipotent differentiation potential. Among the secreted products of MSCs, small extracellular vesicles (sEVs) are currently being explored for their potential as diagnostic and therapeutic tools in clinical settings. To date, ensuring the stable maintenance of optimal sEVs quality remains a substantial challenge, which directly influences their clinical application potential. In this mini-review, This review critically examines the key challenges impeding the development of Good Manufacturing Practice (GMP)-compliant sEVs products (GMP-CPs), organized around three interrelated domains: biological variability arising from heterogeneous donor sources and the intrinsic complexity of sEVs-derived molecular cargo; technical constraints associated with current isolation and analytical characterization methods, including limitations in scalability, reproducibility, and resolution; and evolving regulatory uncertainties stemming from the lack of standardized quality attributes and process definitions. We further evaluate emerging bioengineering strategies, including controlled cargo loading, targeted surface functionalization, and rational sEVs engineering, that seek to mitigate inherent heterogeneity by introducing defined, function-driven modifications. By systematically mapping these scientific, technical, and regulatory challenges alongside corresponding translational approaches, this review aims to serve as a timely and practical reference for researchers and developers advancing GMP-compliant sEVs therapeutics.