Exosomes from miR-21-5p-modified adipose-derived stem cells promote wound healing by regulating M2 macrophage polarization in a rodent model of pressure ulcer
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作者:
Su, Yongsheng
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Peoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R ChinaPeoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R China
Su, Yongsheng
[1
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Huang, Zhibin
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Peoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R ChinaPeoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R China
Huang, Zhibin
[1
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Chen, Yuanwen
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Peoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R ChinaPeoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R China
Chen, Yuanwen
[1
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Deng, Jingcheng
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Peoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R ChinaPeoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R China
Deng, Jingcheng
[1
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Huang, Yubin
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Peoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R ChinaPeoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R China
Huang, Yubin
[1
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Xiong, Wei
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Huazhong Univ Sci & Technol, Union Shenzhen Hosp, Dept Burn & Plast Surg, 89 Taoyuan Rd, Shenzhen 518000, Guangdong, Peoples R ChinaPeoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R China
Xiong, Wei
[2
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机构:
[1] Peoples Hosp Baoan Shenzhen, Dept Burn & Plast Surg, Shenzhen 518000, Peoples R China
[2] Huazhong Univ Sci & Technol, Union Shenzhen Hosp, Dept Burn & Plast Surg, 89 Taoyuan Rd, Shenzhen 518000, Guangdong, Peoples R China
Pressure ulcers represent a significant healthcare burden worldwide. Numerous research has demonstrated the therapeutic potential of adipose-derived stem cell (ADSC)-derived exosomes in promoting wound healing. This study aims to investigate whether exosomes derived from miRNA-modified ADSCs play a role in pressure ulcers by affecting inflammation and macrophage polarization. ADSCs were identified by detecting the surface markers and multilineage differentiation potential. Lentiviruses carrying miR-21-5p were transduced in ADSCs for stable overexpression. Exosomes were extracted from ADSCs and identified. RT-qPCR was employed to detect RNA levels. A mouse model of pressure ulcers was established, followed by injection of exosomes. DiO staining was conducted to assess exosome biodistribution at wound sites. Hematoxylin-eosin and Masson staining were conducted for histological analysis. Immunofluorescence staining was used to evaluate TNF-alpha and IL-6 expression in mouse wound tissues. Western blotting was conducted to evaluate protein levels of macrophage polarization markers in vivo and in vitro. The results revealed that exosomes derived from miR-21-5p-overexpressing ADSCs promoted wound healing and reduced inflammatory cytokine expression in mouse wound tissues. Moreover, exosomal miR-21-5p induced macrophage M2 polarization in both mouse wound tissues and bone marrow-derived macrophages. Mechanistically, exosomal miR-21-5p inhibited NF-kappa B signal transduction in mouse wound tissues. In conclusion, ADSC-derived exosomes promote M2 macrophage polarization and inhibit inflammatory response in pressure ulcers via miR-21-5p delivery.