The development of effective therapeutic strategies for chronic kidney disease (CKD) remains a central focus of contemporary medical research. Mesenchymal stem cells (MSCs) have emerged as a highly promising therapeutic modality for CKD, primarily due to their inherent regenerative and immunomodulatory capabilities. MSCs exert their therapeutic effects predominantly through the transfer of miRNAs via extracellular vesicles (EVs), which orchestrate key cellular pathways involved in renal repair and regeneration. However, critical challenges—including limited differentiation potential, suboptimal survival rates, and inefficient homing capacity—have significantly constrained their clinical translation. As such, enhancing the therapeutic efficacy of MSCs has become a paramount research priority. Recent investigations have demonstrated that preconditioning MSCs can markedly augment their therapeutic performance. Notably, emerging evidence has established a compelling association between herbs and the regulation of miRNA expression in MSC-derived EVs, suggesting novel synergistic interactions between herbs and MSC-based therapies. This review systematically dissects the mechanistic frameworks through which herbs and their bioactive constituents enhance the therapeutic effects of preconditioned MSCs, with a particular emphasis on EV-mediated miRNA cross-talk. The overarching goal is to provide innovative perspectives and translational strategies to facilitate the clinical implementation of preconditioned MSCs in CKD management.
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