Small extracellular vesicles from human bone marrow mesenchymal stromal cells enhance migration and regulate reparative gene expression in dermal fibroblasts.

Studies have shown that mesenchymal stromal cells (MSCs) could secrete a variety of bioactive particles, including small extracellular vesicles (sEVs), that might be a key intermediate to the beneficial paracrine effects of MSC therapy. In this study, we harvested the conditioned medium (CM) from human bone marrow mesenchymal stromal cells (hBM-MSCs) and normal human dermal fibroblasts (NHDFs), fractionated into the sEV fraction and non-small extracellular vesicle (NsEV) fraction, and compared their functions on NHDF migration and proliferation-key processes in wound healing, coupled with transcriptomic analysis through mRNA sequencing to assess gene expression changes in the recipient NHDFs. Our findings show that sEV, NsEV and CM from hBM-MSCs had an overall promotive effect on migration behaviour of NHDFs, but MSC-sEV surpassed the effects of other MSC secretome fractions and their NHDF counterparts (HDF-sEV). Gene ontology analysis revealed enrichment of pathways related to migration, and significant changes in genes within the regulation of proliferation pathway. Our study provides referential significance for the choice of cellular secretome fractions to be used in wound healing studies and insights into the effects of MSC secretome in the migration and proliferation of healthy fibroblasts, besides their effects on gene expression changes.