Abstract
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.
Data availability
All data generated in this study are provided in the articles and available in online supplementary files. All RNA sequencing data reported in this publication have been deposited in NCBI’s Gene Expression Omnibus and are accessible through the GEO accession number: GSE252017.
Abbreviations
- EVs:
-
Extracellular vesicles
- EXs:
-
Exosomes
- MSCs:
-
Mesenchymal stem cells
- UCMSCs:
-
Umbilical cord-derived mesenchymal stem cells
- GO:
-
Gene ontology
- KEGG:
-
Kyoto encyclopedia of genes and genomes
- DEGs:
-
Differentially expressed genes
- GAGE:
-
Generally applicable gene-set enrichment
- DMEM/F12:
-
Dulbecco’s modified eagle medium/Ham’s F-12
- FBS:
-
Fetal bovine serum
- MVs:
-
Microvesicles
- PBS:
-
Phosphate buffer saline
- BCA:
-
Bicinchoninic acid
- PVDF:
-
Polyvinylidene fluoride
- TBST:
-
Tris-buffered saline with tween® 20
- NTA:
-
Nanoparticle tracking analysis
- TEM:
-
Transmission electron microscopy
- FDR:
-
False discovery rate
- BH:
-
Benjamini and Hochbergw
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Acknowledgements
We sincerely thank Dr. Nguyen Thi Nhan for their valuable bioinformatics analysis and review advice.
Funding
This project was funded by the VinIF project code VINIF.2021.DA00193.
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The conception and design of the study: UTTT, NHN, NTMH, and X-HN; Data collection: UTTT, HTTN, QMD, DMV, T-HN, NTMH, THN, X-HN, X-HD, HHD, HTP, QML; Analysis and interpretation of data: UTTT, HTTN, QMD, DMV, THN, NTMH, THN, X-HN, X-HD, HHD, HTP, QML; Manuscript drafting: UTTT, THN, QMD; Manuscript revising, UTTT, X-HN, NTMH, NHN; Final approval: NHN; Funding acquisition: NHN and UTTT.
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Ethical approval for the use of human MSCs from the umbilical cord and dermal fibroblasts was issued by the Vinmec International General Hospital Joint Stock Company’s ethics committee (Ethical approval number: 02/2022/CN-HĐĐĐ VMEC). The umbilical cord tissues were collected from three healthy donors aged 20 to 40, and skin tissues for fibroblasts were collected from women who had undergone plastic surgery. All donors signed written informed consent before donating their samples, and experimental protocols were performed in accordance with the relevant guidelines and regulations and approved by the ethics committee. For the use of animals and all experimental protocols involving animals, the study was approved by the Institutional Review Board at Dinh Tien Hoang Institute of Medicine. The Ethical approval number IRB-A 2203. We confirmed that all experiments and methods used in this study were performed in accordance with relevant regulations and the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guideline.
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Than, U.T.T., Nguyen, H.T.T., Dang, Q.M. et al. mRNA profiling of mesenchymal stem cell-derived exosomes reveals their function in accelerating wound healing. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45267-w
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DOI: https://doi.org/10.1038/s41598-026-45267-w