Email Alerts
RSS
Volume 40 Issue 4
Apr.  2024
Turn off MathJax
Article Contents
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2024  >  40(4): 314-322
Wang HY,Ba T,Zhou B,et al.Effects of applying human umbilical cord mesenchymal stem cell exosomes through different pathways to treat full-thickness skin defect wounds in mice[J].Chin J Burns Wounds,2024,40(4):314-322.DOI: 10.3760/cma.j.cn501225-20231123-00203.
Citation: Wang HY,Ba T,Zhou B,et al.Effects of applying human umbilical cord mesenchymal stem cell exosomes through different pathways to treat full-thickness skin defect wounds in mice[J].Chin J Burns Wounds,2024,40(4):314-322.DOI: 10.3760/cma.j.cn501225-20231123-00203.
shu

Effects of applying human umbilical cord mesenchymal stem cell exosomes through different pathways to treat full-thickness skin defect wounds in mice

doi: 10.3760/cma.j.cn501225-20231123-00203
  • 1.

    Department of Burns, Baogang Hospital of Inner Mongolia, Baotou 014010, China

  • 2.

    Graduate School of Inner Mongolia Medical University, Hohhot 010059, China

  • 3.

    Department of Nutrition, the Fourth Medical Center, PLA General Hospital, Beijing 100037, China

Funds:

Special Project of Science and Technology Action Plan for Prevention and Treatment of Major Diseases 2018ZX-01S-001S01

General Program of Natural Science Foundation of Inner Mongolia Autonomous Region of China 2020MS08022

Inner Mongolia Autonomous Region Science and Technology Innovation Guidance Project CXYD2020BT03

More Information
    Abstract
  •   Objective   To investigate the effects of human umbilical cord mesenchymal stem cell (hUCMSC) exosomes in the treatment of full-thickness skin defect wounds in mice through local wound application, subcutaneous injection at the wound margin, and tail vein injection, and to explore the optimal administration route of hUCMSC exosomes for wound treatment.   Methods   This study was an experimental study. hUCMSC exosomes were extracted from the discarded umbilical cord tissue of three normal delivery women aged 25-35 years in the Department of Obstetrics and Gynecology of Baogang Hospital of Inner Mongolia and successfully identified. Totally 120 male BALB/c mice aged 6-8 weeks were selected, and full-thickness skin defect wounds were prepared on the back of them. According to the random number table, the injured mice were divided into control group (without drug administration), local wound application group, wound margin subcutaneous injection group, and tail vein injection group (with 30 mice in each group). Mice in the latter three groups were given 0.2 mL phosphate buffer solution containing 200 μg hUCMSC exosomes by local wound application, subcutaneous injection at the wound margin, and tail vein injection, respectively. On post injury day (PID) 7, 14, and 21, the general condition of the wound was observed, and the wound healing rate was calculated; the wound tissue was collected, the pathological changes and collagen fibers were observed respectively by hematoxylin-eosin staining and Masson staining, the number of new microvessels was observed by CD31 immunohistochemical staining, and the content of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay. The sample number was 10 in each group at each time point.   Results   On PID 7, 14, and 21, the wounds of mice in the 4 groups all healed gradually, and the wound healing of the mice in wound margin subcutaneous injection group was the best; the wound healing rates of mice in the three administration groups were significantly higher than those in control group ( P<0.05), the wound healing rates of mice in wound margin subcutaneous injection group and tail vein injection group were significantly higher than those in local wound application group ( P<0.05), and the wound healing rates of mice in wound margin subcutaneous injection group were significantly higher than those in tail vein injection group ( P<0.05). On PID 7, 14, and 21, the growth and epithelialization speed of the wound tissue of mice in the three administration groups were significantly accelerated, and the collagen fibers in the wounds of mice in the three administration groups were larger in number and more neatly arranged in comparison with the control group. On PID 7, 14, and 21, under every 200-fold visual field, the number of new microvessels in the wound tissue of mice in local wound application group was 24.1±2.5, 50.7±4.1, and 44.2±2.3, respectively, the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group was 32.2±2.9, 67.5±4.9, and 53.6±3.7, respectively, and the number of new microvessels in the wound tissue of mice in tail vein injection group was 27.8±2.4, 59.1±3.7, and 49.6±2.6, respectively, which was significantly more than 20.6±1.7, 46.7±3.4, and 40.9±2.8 in control group ( P<0.05); the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group and tail vein injection group was significantly more than that in local wound application group ( P<0.05); the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group was significantly more than that in tail vein injection group ( P<0.05). On PID 7, 14, and 21, the content of TNF-α and IL-6 in the wound tissue of mice in the three administration groups was significantly less than that in control group ( P<0.05), the content of TNF-α and IL-6 in the wound tissue of mice in wound margin subcutaneous injection group and tail vein injection group was significantly less than that in local wound application group ( P<0.05), and the content of TNF-α and IL-6 in the wound tissue of mice in wound margin subcutaneous injection group was significantly less than that in tail vein injection group ( P<0.05).   Conclusions   Local wound application, subcutaneous injection at the wound margin, and tail vein injection of hUCMSC exosomes can all promote the wound healing of full-thickness skin defects in mice through alleviating excessive inflammatory response and promoting angiogenesis. Among them, subcutaneous injection at the wound margin has a better therapeutic effect, indicating subcutaneous injection at the wound margin is the optimal administration route for hUCMSC exosomes in wound treatment.

     

    • FullText(HTML)
  • loading
    • References(24)
  • [1]
    ShiY,WangS,LiuD,et al.Exosomal miR-4645-5p from hypoxic bone marrow mesenchymal stem cells facilitates diabetic wound healing by restoring keratinocyte autophagy[J/OL].Burns Trauma,2024,12:tkad058[2023-11-23].https://pubmed.ncbi.nlm.nih.gov/38250706/.DOI: 10.1093/burnst/tkad058.
    [2]
    曹学新,张永磊,赵树青,等.股后肌瓣联合股后皮神经营养血管皮瓣及闭式灌洗治疗Ⅳ期坐骨结节压疮的临床效果[J].中华烧伤与创面修复杂志,2024,40(2):159-164.DOI: 10.3760/cma.j.cn501225-20231017-00115.
    [3]
    罗雅婷,解婧,许涛,等.人脐带间充质干细胞来源外泌体对小鼠压疮的治疗作用及机制[J].海军军医大学学报,2022,43(6):622-632.DOI: 10.16781/j.CN31-2187/R.20220373.
    [4]
    王乐融,杨静,姬凯,等.骨髓间质干细胞培养液对创面愈合的作用及机制[J].中国美容整形外科杂志,2023,34(8):494-497.DOI: 10.3969/j.issn.1673-7040.2023.08.014.
    [5]
    牛少辉,李贝,方毅娜,等.不同细胞来源的外泌体在糖尿病足创面修复中的作用机制和干预前景[J/CD].中国血管外科杂志(电子版),2023,15(1):83-87.DOI: 10.3969/j.issn.1674-7429.2023.01.020.
    [6]
    沈才齐,李强,金培生,等.人脐带间充质干细胞治疗糖尿病创面效果及其在体内存活、定植研究[J].徐州医科大学学报,2022,42(1):25-29.DOI: 10.3969/j.issn.2096-3882.2022.01.005.
    [7]
    范龙坤,刘春晖,赵钰佳,等.骨髓间充质干细胞来源外泌体通过TGF-β1/smad2/3信号通路抑制增生性瘢痕的机制研究[J].河北医科大学学报,2023,44(8):876-882,899.DOI: 10.3969/j.issn.1007-3205.2023.08.002.
    [8]
    张雨薇,牛菊红,刘川川,等.用聚乙二醇沉淀法提取脐带间充质干细胞源外泌体抑制PASMCs增殖[J].中国高原医学与生物学杂志,2023,44(4):217-226.DOI: 10.13452/j.cnki.jqmc.2023.04.001.
    [9]
    陈瑞婧,冯韬锦,程实,等.3D培养人脐带间充质干细胞来源的外泌体对成骨细胞分化的作用[J].解放军医学杂志,2023,48(4):411-419.DOI: 10.11855/j.issn.0577-7402.2023.04.0411.
    [10]
    张静莹,李自伊,刘小川,等.尾静脉注射骨髓间充质干细胞修复衰老小鼠颅骨损伤[J].中国组织工程研究,2022,26(25):3944-3950.
    [11]
    SenCK.Human wound and its burden: updated 2020 compendium of estimates[J].Adv Wound Care (New Rochelle),2021,10(5):281-292.DOI: 10.1089/wound.2021.0026.
    [12]
    KalluriR,LeBleuVS.The biology, function, and biomedical applications of exosomes[J].Science,2020,367(6478):eaau6977.DOI: 10.1126/science.aau6977.
    [13]
    陈凤,杨敏,李彦洁,等.人脐带间充质干细胞的分离培养及多向分化潜能研究[J].生物学杂志,2021,38(5):82-85,90.DOI: 10.3969/j.issn.2095-1736.2021.05.082.
    [14]
    简喜超,邓呈亮.微小RNA工程化外泌体在糖尿病创面中的作用研究进展[J].中华烧伤与创面修复杂志,2024,40(2):190-195.DOI: 10.3760/cma.j.cn501225-20230721-00011.
    [15]
    徐崔博诚,徐正保,余承洋,等.负载Wharton's Jelly源间充质干细胞来源外泌体的水凝胶可促进小鼠创面修复[J].浙江大学学报(医学版),2023,52(6):766-776.DOI: 10.3724/zdxbyxb-2023-0316.
    [16]
    PiipponenM,LiD,LandénNX.The immune functions of keratinocytes in skin wound healing[J]. Int J Mol Sci,2020,21(22):8790.DOI: 10.3390/ijms21228790.
    [17]
    蔡振林,曾冉,王墨涵,等.肝素溶液持续湿敷对头颈部创口Ⅰ期愈合及初期瘢痕形成的影响[J].遵义医科大学学报,2023,46(5):492-497.
    [18]
    王圆圆,张琪.长链非编码RNA在脓毒症多器官功能障碍中的研究进展[J/CD].中华危重症医学杂志(电子版),2021,14(2):161-164.DOI: 10.3877/cma.j.issn.1674-6880.2021.02.014.
    [19]
    AnT,ChenY,TuY,et al.Mesenchymal stromal cell-derived extracellular vesicles in the treatment of diabetic foot ulcers: application and challenges[J].Stem Cell Rev Rep,2021,17(2):369-378.DOI: 10.1007/s12015-020-10014-9.
    [20]
    LiuW,YuM,XieD,et al.Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway[J].Stem Cell Res Ther,2020,11(1):259.DOI: 10.1186/s13287-020-01756-x.
    [21]
    MaziniL,RochetteL,HamdanY,et al.Skin immunomodulation during regeneration: emerging new targets[J].J Pers Med,2021,11(2):85.DOI: 10.3390/jpm11020085.
    [22]
    李松莲,范洪桥,刘丽芳,等.抑制Notch信号通路减少增生性瘢痕的血管生成[J].中南大学学报(医学版),2021,46(11):1195-1202.DOI: 10.11817/j.issn.1672-7347.2021.210234.
    [23]
    付文,王向臣,王延桂,等.脂肪源性间充质干细胞外泌体在大鼠全层皮肤缺损创面愈合中的机制研究[J].组织工程与重建外科杂志,2023,19(4):342-351,379.DOI: 10.3969/j.issn.1673-0364.2023.04.003.
    [24]
    王江文,易阳艳,朱元正,等.脂肪干细胞来源外泌体促进糖尿病小鼠创面愈合的实验研究[J].中国修复重建外科杂志,2020,34(1):124-131.DOI: 10.7507/1002-1892.201903058.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(5)  / Tables(3)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (66) PDF downloads(17) Cited by()
    Proportional views
    Related

    Copyright © Chinese Journal of Burns京ICP备07035254号-14

    E-mail：shaoshangzazhi@163.com

    Website：https://zhsszz.xml-journal.net/

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return