{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:25:33Z","timestamp":1790573133853,"version":"4.1.0"},"reference-count":117,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":290,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"publisher","award":["82172211"],"award-info":[{"award-number":["82172211"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"publisher","award":["81830064"],"award-info":[{"award-number":["81830064"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"publisher","award":["82172231"],"award-info":[{"award-number":["82172231"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"publisher","award":["81901971"],"award-info":[{"award-number":["81901971"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Programs of China","award":["2022YFA1104303"],"award-info":[{"award-number":["2022YFA1104303"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2019-I2M-5-059"],"award-info":[{"award-number":["2019-I2M-5-059"]}]},{"name":"Military Medical Research and Development Projects","award":["AWS17J005"],"award-info":[{"award-number":["AWS17J005"]}]},{"name":"Military Medical Research and Development Projects","award":["2019\u2013126"],"award-info":[{"award-number":["2019\u2013126"]}]},{"name":"Military Medical Science and Technology Youth Training Program","award":["21QNPY128"],"award-info":[{"award-number":["21QNPY128"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Persistent hyperglycaemia in diabetes causes functional abnormalities of human dermal fibroblasts (HDFs), partially leading to delayed skin wound healing. Extracellular vesicles (EVs) containing multiple pro-healing microRNAs (miRNAs) have been shown to exert therapeutic effects on diabetic wound healing. The present study aimed to observe the effects of EVs derived from placental mesenchymal stem cells (P-MSC-EVs) on diabetic wound healing and high glucose (HG)-induced senescent fibroblasts and to explore the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>P-MSC-EVs were isolated by differential ultracentrifugation and locally injected into the full-thickness skin wounds of diabetic mice, to observe the beneficial effects on wound healing in vivo by measuring wound closure rates and histological analysis. Next, a series of assays were conducted to evaluate the effects of low (2.28 x 1010 particles\/ml) and high (4.56 x 1010 particles\/ml) concentrations of P-MSC-EVs on the senescence, proliferation, migration, and apoptosis of HG-induced senescent HDFs in vitro. Then, miRNA microarrays and real-time quantitative PCR (RT\u2013qPCR) were carried out to detect the differentially expressed miRNAs in HDFs after EVs treatment. Specific RNA inhibitors, miRNA mimics, and small interfering RNA (siRNA) were used to evaluate the role of a candidate miRNA and its target genes in P-MSC-EV-induced improvements in the function of HG-induced senescent HDFs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Local injection of P-MSC-EVs into diabetic wounds accelerated wound closure and reduced scar widths, with better-organized collagen deposition and decreased p16INK4a expression. In vitro, P-MSC-EVs enhanced the antisenescence, proliferation, migration, and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent manner. MiR-145-5p was found to be highly enriched in P-MSC-EVs. MiR-145-5p inhibitors effectively attenuated the P-MSC-EV-induced functional improvements of senescent fibroblasts. MiR-145-5p mimics simulated the effects of P-MSC-EVs on functional improvements of fibroblasts by suppressing the expression of cyclin-dependent kinase inhibitor 1A and activating the extracellular signal regulated kinase (Erk)\/protein kinase B (Akt) signaling pathway. Furthermore, local application of miR-145-5p agomir mimicked the effects of P-MSC-EVs on wound healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest that P-MSC-EVs accelerate diabetic wound healing by improving the function of senescent fibroblasts through the transfer of miR-145-5p, which targets cyclin-dependent kinase inhibitor 1A to activate the Erk\/Akt signaling pathway. P-MSC-EVs are promising therapeutic candidates for diabetic wound treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/burnst\/tkad010","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T08:25:59Z","timestamp":1692865559000},"source":"Crossref","is-referenced-by-count":44,"title":["P-MSC-derived extracellular vesicles facilitate diabetic wound healing via miR-145-5p\/ CDKN1A-mediated functional improvements of high glucose-induced senescent fibroblasts"],"prefix":"10.1093","volume":"11","author":[{"given":"Jianlong","family":"Su","sequence":"first","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital , 51 Fucheng Road, Haidian District, Beijing 100048 , China"},{"name":"School of Medicine, NanKai University , 94 Weijin Road, Nankai District, Tianjin 300071 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wei","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital , 51 Fucheng Road, Haidian District, Beijing 100048 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Ma","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital , 51 Fucheng Road, Haidian District, Beijing 100048 , China"},{"name":"Research Unit of Trauma Care , Tissue Repair and Regeneration, , 2019RU051, 51 Fucheng Road, Haidian District, Beijing 100048 , China"},{"name":"Chinese Academy of Medical Sciences , Tissue Repair and Regeneration, , 2019RU051, 51 Fucheng Road, Haidian District, Beijing 100048 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital , 51 Fucheng Road, Haidian District, Beijing 100048 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhi","family":"Hu","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital , 51 Fucheng Road, Haidian District, Beijing 100048 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Meng","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital , 51 Fucheng Road, Haidian District, Beijing 100048 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiankun","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital , 51 Fucheng Road, Haidian District, Beijing 100048 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Burn and Plastic Surgery, Zhongda Hospital Affiliated Southeast University , Dingjiaqiao 87, Gulou District, Nanjing 210009 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital , 51 Fucheng Road, Haidian District, Beijing 100048 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Wound Repair , Institute of Wound Repair and Regeneration Medicine, Southern University of Science and Technology Hospital, , 6019 Xililiuxian Road, Nanshan District, Shenzhen 518055 , China"},{"name":"Southern University of Science and Technology School of Medicine , Institute of Wound Repair and Regeneration Medicine, Southern University of Science and Technology Hospital, , 6019 Xililiuxian Road, Nanshan District, Shenzhen 518055 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Fu","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General 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