Stem cell-derived exosomes in the therapy of renal diseases: a comprehensive review

Abstract

Chronic kidney disease (CKD) represents a growing global public health challenge. Current treatments, including pharmacological therapy, immunosuppression, and renal replacement therapy, mainly aim to slow disease progression rather than restore damaged renal tissue, and their efficacy remains limited in many patients. Although stem cell-based therapies have shown regenerative potential, their clinical application is constrained by poor cell survival, limited engraftment, immunogenicity, and potential safety concerns. Stem cell-derived exosomes (SC-exosomes) have therefore attracted increasing attention as a potential cell-free therapeutic strategy. These nanoscale extracellular vesicles can transfer bioactive cargoes, including proteins, lipids, messenger RNAs (mRNAs), and microRNAs (miRNAs), to recipient cells and thereby mediate intercellular communication. Compared with parental stem cell transplantation, SC-exosomes may offer several advantages, including lower immunogenicity, reduced tumorigenic risk, relative stability, and the potential to cross certain biological barriers. This comprehensive review summarizes current research on SC-exosomes in renal diseases, with emphasis on their biological characteristics, therapeutic mechanisms, preclinical evidence, and translational challenges. SC-exosomes may contribute to renal repair by promoting cell survival and regeneration, suppressing inflammation, apoptosis, oxidative stress, and fibrosis, and modulating immune and microvascular responses. We also discuss their potential relevance in multiple renal conditions, including acute kidney injury (AKI), CKD, diabetic nephropathy (DN), and other kidney diseases, as well as the use of exosomal cargoes as candidate diagnostic or prognostic biomarkers. Finally, we outline emerging opportunities and unresolved challenges in this field, including engineered exosomes, targeted delivery, exosome heterogeneity, dose optimization, large-scale production, purification, quality control, and long-term safety. Further standardized preclinical studies and well-designed clinical trials are needed before SC-exosome-based approaches can be translated into routine clinical application.