mRNA profiling of mesenchymal stem cell-derived exosomes reveals their function in accelerating wound healing

Extracellular vesicles (EVs) are emerging as innovative tools for regenerative and therapeutic applications, including wound healing, owing to their ability to encapsulate bioactive agents from their parent cells. In this study, we profiled the transcriptome of umbilical cord mesenchymal stem cell (UCMSC)-derived exosomes (EXs) using RNA-seq and explored the functional roles of their transcriptome, particularly in cutaneous wound repair. We detected 4,578 protein-coding genes in UCMSC-derived EXs, of which 2,004 were upregulated, and 2,574 were downregulated relative to their secreting cells. Notably, many EX-enriched genes were associated with wound-healing biology, and pathway analysis revealed that upregulated exosomal genes were involved in GO terms and KEGG pathways related to DNA replication, ribosome function, cell cycle regulation, and pyrimidine metabolism. To validate UCMSC-EX’s capability for wound healing predicted through in silico analyses, we further assessed EX penetration into the dermis, cellular uptake, and therapeutic efficacy in a burned mouse model. UCMSC-derived EXs efficiently penetrated human dermal tissue, were internalized by fibroblasts, and promoted fibroblast and keratinocyte proliferation and migration in 2D culture. In vivo, EX treatment accelerated wound closure, particularly during the early stages of healing. Overall, our findings demonstrate selective mRNA enrichment in UCMSC-derived EXs and highlight their promising therapeutic potential in cutaneous wound healing.