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槲皮素预处理人脐带间充质干细胞来源的外泌体通过调节宿主-微生物群的相互作用促进糖尿病皮肤伤口的愈合
Authors Wu S, Zhou Z, Li Y, Wu R, Jiang J
Received 9 September 2024
Accepted for publication 20 November 2024
Published 26 November 2024 Volume 2024:19 Pages 12557—12581
DOI https://doi.org/10.2147/IJN.S491471
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. RDK Misra
Shuhui Wu,1,* Zhongsheng Zhou,1,* Yang Li,1 Ronghui Wu,2 Jinlan Jiang1
1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jinlan Jiang, Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, People’s Republic of China, Email jiangjinlan@jlu.edu.cn
Background: Owing to the distinctive advantages of mesenchymal stem cell-derived exosomes (MSCs-exo), these vesicles have emerged as a pivotal research focus in regenerative medicine, surpassing their MSC counterparts. Quercetin (Qr), widely recognized for its potent anti-inflammatory and antioxidant activities, demonstrates substantial potential in enhancing tissue repair processes. This study delves into the role of quercetin-pretreated MSC-derived exosomes (MSCsQr-exo) in accelerating the healing of diabetic wounds.
Methods: MSCsQr-exo were isolated from quercetin-pretreated MSCs and applied to fibroblasts to evaluate changes in cell function. An in vitro DSW rat model was also developed, and the rats were treated with MSCsQr-exo to assess wound healing progression. Fecal samples were collected for 16S rRNA sequencing and untargeted metabolomics to analyze changes in gut microbiota and metabolic profiles.
Results: MSCsQr-exo significantly enhanced fibroblast proliferation and migration while improving the therapeutic efficacy of MSCs-exo in DSW treatment. Gut microbiota and metabolomic analyses revealed marked changes in DSW rats, with MSCsQr-exo effectively alleviating dysbiosis. MSCsQr-exo upregulated Faecalibacterium abundance and regulated arachidonic acid metabolism in both the arachidonic and linoleic acid pathways. Firmicutes and Enterobacteriaceae influenced the arachidonic acid pathway by modulating 14.15-EET expression levels.
Conclusion: MSCsQr-exo facilitate DSW wound healing through modulation of dysbiotic gut microbiota linked to DSW pathology. This discovery offers novel therapeutic avenues and research trajectories for enhancing DSW recovery.
Keywords: mesenchymal stem cells, exosomes, quercetin, diabetic skin wound, gut microbiota, metabolites