Volume 6, Issue 3 (2025) – 17 articles
Cover Picture:
Tubular epithelial cells (TECs) are central mediators in both injury and repair processes in kidney disease, rendering them a critical therapeutic target for mitigating kidney disease (CKD). Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have gained increasing attention as cell-free therapeutic agents, capable of delivering bioactive cargos–including miRNAs, proteins, and lipids–that modulate inflammation, apoptosis, oxidative stress, and fibrosis. This review, entitled "Beyond preclinical promise: can mesenchymal stromal cell-derived extracellular vesicles reliably target tubular epithelial cells?", offers a comprehensive and critical analysis of the evidence supporting the targeting of TECs by MSC-EVs. It integrates in vitro and in vivo data to elucidate mechanisms of MSC-EV uptake via ligand–receptor interactions such as those involving CD44 and KIM-1, and discuss how factors such as EV biodistribution, administration routes, and isolation methods affect targeting efficiency. Furthermore, the review highlights ongoing challenges related to EV heterogeneity, nonspecific organ accumulation, and methodological inconsistencies that hinder translational progress. Finally, emerging strategies combining active and passive targeting, along with engineering approaches to functionalize EVs with TEC-specific ligands, are discussed as promising avenues to enhance renal specificity and therapeutic efficacy in MSC-EV–based interventions for kidney injury.
Tubular epithelial cells (TECs) are central mediators in both injury and repair processes in kidney disease, rendering them a critical therapeutic target for mitigating kidney disease (CKD). Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have gained increasing attention as cell-free therapeutic agents, capable of delivering bioactive cargos–including miRNAs, proteins, and lipids–that modulate inflammation, apoptosis, oxidative stress, and fibrosis. This review, entitled "Beyond preclinical promise: can mesenchymal stromal cell-derived extracellular vesicles reliably target tubular epithelial cells?", offers a comprehensive and critical analysis of the evidence supporting the targeting of TECs by MSC-EVs. It integrates in vitro and in vivo data to elucidate mechanisms of MSC-EV uptake via ligand–receptor interactions such as those involving CD44 and KIM-1, and discuss how factors such as EV biodistribution, administration routes, and isolation methods affect targeting efficiency. Furthermore, the review highlights ongoing challenges related to EV heterogeneity, nonspecific organ accumulation, and methodological inconsistencies that hinder translational progress. Finally, emerging strategies combining active and passive targeting, along with engineering approaches to functionalize EVs with TEC-specific ligands, are discussed as promising avenues to enhance renal specificity and therapeutic efficacy in MSC-EV–based interventions for kidney injury.
