Abstract
Acute kidney injury (AKI) remains a significant clinical challenge, characterized by rapid kidney dysfunction with potential progression to chronic kidney disease. Mesenchymal stem cells (MSCs) offer promising therapeutic potential due to their regenerative, immunomodulatory and anti‑inflammatory capabilities. Despite these advantages, clinical translation is hampered by low MSCs retention, limited cell survival and suboptimal secretion of therapeutic factors in injured renal tissues. Recent research efforts have introduced innovative strategies to optimize MSCs effectiveness, including various preconditioning approaches (hypoxia, chemical/drug‑based and biological cytokines), advanced three‑dimensional cell culture methods (hydrogels and spheroids), genetic modification techniques and improved delivery routes. The present review summarizes current advancements, underlying mechanisms and therapeutic outcomes associated with these novel strategies to enhance MSCs efficacy in AKI, highlighting their clinical potential and guiding future translational research directions.