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Abstract <p>This study was aimed to determine the effect of a mesenchymalstromal cell-conditioned medium (MSC-CM) derived from a cultureof autologous bone marrow MSCs grown under moderately hypoxic conditions(10% O<sub>2</sub>) on the immune regulation of uterinewall healing in Sprague-Dawley rats after injury (a full-thicknesssurgical incision). In the first group of animals (<i>n</i> = 14), the injured uterine wall regionwas treated with an MSC-CM preparation prior to suturing, whilein the second (control) group (<i>n</i> =14), the incision was left untreated. The healing zone was examinedon day 5 and day 15 post-surgery using histological (hematoxylin/eosinand Mallory’s trichrome staining) and immunohistochemical (CD68+and FABP4+ macrophages) methods, as well as real-time polymerase chainreaction (mRNA expression of pro-inflammatory IL-1β, IL-6 and anti-inflammatoryIL-4, IL-10 cytokines). The area of the healing zone in the treatedgroup was smaller compared to the control at all time points ofobservation (<i>p</i> &lt; 0.05).On day 5, IL-4 and IL-10 expression was lower in the treated group thanin the control, while on day 15, IL-1β expression was lower in thecontrol group. From day 5 to day 15, IL-1β, IL-4, IL-6, and IL-10expression decreased in the control group (<i>p</i> &lt;0.05), while exhibiting no significant differences in the treatedgroup (<i>p</i> &lt; 0.05). By day15, the number of CD68+ cells decreased in the treated group comparedto day 5, while being lower than in the control group. By day 15,FABP4+ cell clusters nearly disappeared in the injured myometrialuterine wall layer in both groups, except for two animals in thecontrol, however, in the injured perimetrial layer, their numberincreased in the control, while decreasing in the treated group,where it was significantly lower than in the control group. Thus,uterine wound treatment in rats with MSC culture components (MSC-CM)led to a reduction in the uterine wall injury, a decrease in theinflammatory response, and the acceleration of uterine wall healingafter injury.</p>

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Immunological Effect of Moderately Hypoxic Mesenchymal Stromal Cell Culture Conditions on Uterine Healing in Rats

  • 期刊论文

  • 发表日期：

    2025年5月1日

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  • N. B. Tikhonova,
  • A. A. Temnov,
  • V. V. Aleksankina,
  • T. V. Fokina,
  • A. P. Aleksankin,
  • A. N. Sklifas,
  • E. V. Kuznetsova,
  • A. P. Milovanov,
  • L. M. Mikhaleva

摘要

Abstract

This study was aimed to determine the effect of a mesenchymalstromal cell-conditioned medium (MSC-CM) derived from a cultureof autologous bone marrow MSCs grown under moderately hypoxic conditions(10% O2) on the immune regulation of uterinewall healing in Sprague-Dawley rats after injury (a full-thicknesssurgical incision). In the first group of animals (n = 14), the injured uterine wall regionwas treated with an MSC-CM preparation prior to suturing, whilein the second (control) group (n =14), the incision was left untreated. The healing zone was examinedon day 5 and day 15 post-surgery using histological (hematoxylin/eosinand Mallory’s trichrome staining) and immunohistochemical (CD68+and FABP4+ macrophages) methods, as well as real-time polymerase chainreaction (mRNA expression of pro-inflammatory IL-1β, IL-6 and anti-inflammatoryIL-4, IL-10 cytokines). The area of the healing zone in the treatedgroup was smaller compared to the control at all time points ofobservation (p < 0.05).On day 5, IL-4 and IL-10 expression was lower in the treated group thanin the control, while on day 15, IL-1β expression was lower in thecontrol group. From day 5 to day 15, IL-1β, IL-4, IL-6, and IL-10expression decreased in the control group (p <0.05), while exhibiting no significant differences in the treatedgroup (p < 0.05). By day15, the number of CD68+ cells decreased in the treated group comparedto day 5, while being lower than in the control group. By day 15,FABP4+ cell clusters nearly disappeared in the injured myometrialuterine wall layer in both groups, except for two animals in thecontrol, however, in the injured perimetrial layer, their numberincreased in the control, while decreasing in the treated group,where it was significantly lower than in the control group. Thus,uterine wound treatment in rats with MSC culture components (MSC-CM)led to a reduction in the uterine wall injury, a decrease in theinflammatory response, and the acceleration of uterine wall healingafter injury.