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

Wang Hongyu; Ba Te; Zhou Biao; Yan Zengqiang; Wang Ruijia; Liu Lingying

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

Volume 40 Issue 4

Apr. 2024

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Article Navigation > CHINESE JOURNAL OF BURNS AND WOUNDS > 2024 > 40(4): 314-322

Yang Minlie, Zhou Xiaojin, Zhu Yugang, et al. Clinical efficacy and influencing factors of different modes of continuous negative pressure wound therapy on venous ulcer wounds of lower limbs[J]. Chin j Burns, 2020, 36(12): 1149-1158. Doi: 10.3760/cma.j.cn501120-20200316-00173

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.

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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

Corresponding author: Liu Lingying, Email: liulingyingyisheng@163.com
Received Date: 2023-11-23

Abstract

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.
- Wounds and injuries,
- Skin,
- Mesenchymal stem cells,
- Exosomes,
- Inflammation,
- Neovascularization, pathologic,
- Wound repair,
- Route of administration

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References

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