Adipose mesenchymal stem cell-derived nanovesicles as a therapeutic strategy for oral mucosal regeneration after chemotherapy in a rat model

Chemotherapy-induced oral mucositis (CIOM) is a debilitating complication with limited therapeutic options. Mesenchymal stem cells (MSCs) promote tissue repair through paracrine signaling, and stem cell-derived nanovesicles (SC-NVs) have emerged as a scalable, cell-free therapeutic alternative. However, the regenerative potential of SC-NVs has not been investigated in the context of CIOM. This study evaluated the regenerative effects of SC-NVs derived from human adipose-derived MSCs (AD MSCs) in vitro assays and a rat CIOM model. Transcriptomic profiling showed enrichment of wound healing and angiogenesis-related genes in AD MSCs. SC-NVs were produced by serial extrusion and characterized by nanoscale size and reproducible protein content. Following intralesional injection, SC-NVs localized to the ulcer bed and remained detectable for up to 5 days. SC-NV treatment enhanced epithelial regeneration, promoted angiogenesis, and reduced inflammatory markers in vitro and in vivo. These findings support SC-NVs as a scalable, cell-free therapeutic platform for CIOM.