Beyond preclinical promise: can mesenchymal stromal cell-derived extracellular vesicles reliably target tubular epithelial cells?

Kidney disease, encompassing both acute kidney injury (AKI) and chronic kidney disease (CKD), represents a major global health challenge. A pivotal aspect of the pathogenesis of these conditions is damage to renal tubular epithelial cells (TECs), which contributes to maladaptive repair mechanisms and fibrosis. Due to their essential role, TECs are regarded as a promising target for innovative therapeutic strategies. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have attracted increasing attention for their therapeutic potential in kidney disease, with extensive literature documenting their beneficial effects on TEC damage through targeted mechanisms. In this review, we critically examine the existing literature on the targeting of TECs by MSC-EVs in both in vitro and in vivo settings. Furthermore, we highlight the limitations and potential of MSC-EV-based strategies for TEC targeting, aiming to provide insights for future clinical trials and therapeutic applications.