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However, ischemia-reperfusion (IR) injury can affect the success rate of skin flap transplantation. We used a free abdomen flap rat model to explore the protective effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-exosomes) against the IR injury of the skin flap. Exosomes were injected through the tail vein and the flaps were observed and obtained on day 7. We observed that BMSCs-exosomes significantly reduced the necrotic lesions of the skin flap. Furthermore, BMSCs-exosomes relieved oxidative stress and reduced the levels of inflammatory factors. Apoptosis was evaluated via the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and Western blot analysis of Bax, Bcl-2. Simultaneously, BMSCs-exosomes promoted the formation of new blood vessels in the IR flap, as confirmed by the increased expression level of VEGFA and the fluorescence co-staining of CD31 and PCNA. Additionally, BMSCs-exosomes considerably increased proliferation and migration of human umbilical vein endothelial cells and promoted angiogenesis in vitro. BMSCs-exosomes could be a promising cell-free therapeutic candidate to reduce IR injury and promote the survival of skin flaps.<\/jats:p>","DOI":"10.3390\/life12101567","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T20:49:31Z","timestamp":1665348571000},"page":"1567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Ischemia-Reperfusion Injury and Promote Survival of Skin Flaps in Rats"],"prefix":"10.3390","volume":"12","author":[{"given":"Qifang","family":"Niu","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China"},{"name":"Department of Oral and Maxillofacial Surgery, Beijing XingYe Stomatological Hospital, Beijing 102600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyue","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1952-6734","authenticated-orcid":false,"given":"Zhien","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9508-1098","authenticated-orcid":false,"given":"Zhengxue","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1001\/jamaoto.2016.2981","article-title":"Optimal Perioperative Care in Major Head and Neck Cancer Surgery with Free Flap Reconstruction: A Consensus Review and Recommendations from the Enhanced Recovery After Surgery Society","volume":"143","author":"Dort","year":"2017","journal-title":"JAMA Otolaryngol. 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