Differential Wound Healing Potential of Tonsil Parenchymal and Epithelial Mesenchymal Stromal Cell-Derived Exosomes.

BACKGROUND

The biological characteristics of mesenchymal stromal cells (MSCs) and their exosomes can vary depending on the tissue layer of origin, potentially influencing their regenerative capacity. This study aimed to determine whether exosomes derived from epithelial (TE-MSCs) and parenchymal (TP-MSCs) layers of human tonsils exhibit distinct therapeutic effects in oral mucositis (OM).

METHODS

MSCs Were isolated from the epithelial (TE-MSCs) and parenchymal (TP-MSCs) layers of human tonsils. Exosomes were characterized and tested for regenerative and anti-inflammatory effects in vitro and in a 5-FU-induced OM hamster model

RESULTS

Both TP-MSCs and TE-MSCs exhibited typical MSC phenotypes and multipotency comparable to BMSCs. Transcriptomic profiling revealed distinct layer-specific features, with TE-MSCs enriched in developmental and morphogenetic pathways. TE-MSC-derived exosomes (TE-MSC-Exo) showed enhanced wound closure, downregulation of IL-1β and TNF-α, and selective induction of HGF and ICAM-1 expression. In vivo, TE-MSC-Exo treatment resulted in the smallest mean wound size and most complete re-epithelialization among experimental groups.

CONCLUSION

Exosomes derived from tonsil MSCs effectively promote epithelial regeneration in OM, with TE-MSC-Exo exhibiting enhanced therapeutic potential. These findings highlight the importance of MSC layer origin in defining exosome function and suggest that TE-MSC-Exo may serve as a promising platform for exosome-based mucosal repair therapies.