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Volume 41 Issue 9
Sep.  2025
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2025  >  41(9): 867-876
Liu ZY,Pan WJ,Wang Z,et al.Effects of the pretreatment of human umbilical cord mesenchymal stem cells with tumor necrosis factor-α and interleukin-1β on the healing of ischemic wounds in rats[J].Chin J Burns Wounds,2025,41(9):867-876.DOI: 10.3760/cma.j.cn501225-20241008-00377.
Citation: Liu ZY,Pan WJ,Wang Z,et al.Effects of the pretreatment of human umbilical cord mesenchymal stem cells with tumor necrosis factor-α and interleukin-1β on the healing of ischemic wounds in rats[J].Chin J Burns Wounds,2025,41(9):867-876.DOI: 10.3760/cma.j.cn501225-20241008-00377.
shu

Effects of the pretreatment of human umbilical cord mesenchymal stem cells with tumor necrosis factor-α and interleukin-1β on the healing of ischemic wounds in rats

doi: 10.3760/cma.j.cn501225-20241008-00377

  • Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China

Funds:

Key Program of National Natural Science Foundation of China 82472567

Guizhou Provincial Department of Science and Technology Project 2024314

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    Abstract
  •   Objective  To investigate the effects of the pretreatment of human umbilical cord mesenchymal stem cells (hUMSCs) with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) on the healing of ischemic wounds in rats.  Methods  This study was an experimental research. The umbilical cord tissue was collected from three healthy full-term neonates delivered by cesarean section from delivery women aged 22-35 years in the Affiliated Hospital of Zunyi Medical University between December 2022 and April 2023. The hUMSCs were isolated, and after the scratch test, the cells were divided into pretreatment group pretreated with TNF-α and IL-1β of both final mass concentrations of 20 ng/mL and control group cultured conventionally according to the random number table method (the same grouping method below). The cell migration rates were calculated at 8, 16, and 32 h after scratch, with sample size of 3. Five 9-week-old male Sprague-Dawley (SD) rats were used to construct a bipedicled flap with an area of 11.0 cm×2.5 cm on the back, two ischemic wounds with diameter of 0.6 cm were created on the flaps, and two non-ischemic wounds with diameter of 0.6 cm were created on normal dorsal skin. The wound healing rates were calculated at 6, 12, and 18 d after modeling to validate the reliability of the ischemic wound model. Another 15 male SD rats aged 9 weeks were subjected to the same ischemic wound model as above and divided into pretreated hUMSC group, conventional hUMSC group, and phosphate-buffered saline (PBS) group, with 5 rats in each group, which were respectively injected with pretreated hUMSCs as before, conventionally cultured hUMSCs, and PBS at the wound margin. The wound healing rates were calculated at 3, 6, 9, and 12 d after injection. At 12 d after injection, the wound tissue was collected for hematoxylin-eosin staining to assess epithelialization of wounds, for Masson staining to observe collagen fiber formation in wound tissue, and for immunofluorescence staining to detect the number of blood vessels, arginase-1 (Arg1)-positive cells, and inducible nitric oxide synthase (iNOS)-positive cells in wound tissue.  Results  At 16 and 32 h after scratch, the cell migration rates in pretreatment group were significantly higher than those in control group (with Z values of -2.61 and -2.61, respectively, P<0.05). At 6, 12, and 18 d after modeling, the healing rates of non-ischemic wounds of rats were significantly higher than those of ischemic wounds (with Z values of 2.61, 2.79, and 2.79, respectively, P<0.05). At 6, 9, and 12 d after injection, the wound healing rates in pretreated hUMSC group of rats were 6.83% (3.13%, 12.22%), 66.83% (60.09%, 95.68%), and 96.98% (91.67%, 99.80%), respectively, which were significantly higher than 1.54% (0.30%, 3.47%), 1.54% (0.60%, 5.90%), and 3.08% (0.90%, 7.64%) in PBS group (with Z values of 7.60, 9.40, and 10.00, respectively, P<0.05). At 9 d after injection, the wound healing rate in pretreated hUMSC group of rats was significantly higher than 5.86% (4.72%, 8.12%) in conventional hUMSC group (Z=5.60, P<0.05). At 12 d after injection, the wound epithelialization basically completed in pretreated hUMSC group of rats, and the collagen fiber formation in wound tissue was markedly better than that in conventional hUMSC group and PBS group. At 12 d after injection, the number of blood vessels and Arg1-positive cells in wound tissue in pretreated hUMSC group of rats was significantly more than that in conventional hUMSC group and PBS group (P<0.05), and the number of blood vessels and Arg1-positive cells in wound tissue in conventional hUMSC group of rats was significantly more than that in PBS group (P<0.05); the number of iNOS-positive cells in pretreated hUMSC group of rats was significantly less than that in conventional hUMSC group and PBS group (with both P values <0.05), and the number of iNOS-positive cells in conventional hUMSC group of rats was significantly less than that in PBS group (P<0.05).  Conclusions  The pretreatment of hUMSCs with TNF-α and IL-1β can enhance the abilities of migration, immunomodulation, and promoting angiogenesis of the cells, thereby promoting the healing of ischemic wounds.

     

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