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脐带间充质干细胞接种于小肠黏膜下层修复子宫内膜损伤。

Umbilical Cord Mesenchymal Stem Cells Seeded on Small Intestinal Submucosa to Repair the Uterine Wall Injuries.

机构信息

Division of Biomaterials, Department of Medical Devices, National Institute for Food and Drug Control, Beijing, China.

出版信息

Tissue Eng Part C Methods. 2022 Nov;28(11):589-598. doi: 10.1089/ten.TEC.2022.0007. Epub 2022 Oct 26.

Abstract

The effectiveness of tissue engineering materials combining porcine small intestine submucosa (SIS) and umbilical cord mesenchymal stem cells (UC-MSCs) on uterine injury in female rat after full-thickness uterine resection was evaluated as a basis for clinical treatment of postoperative uterine injury. After complex culture with SIS and UC-MSCs, cell adhesion, growth, and proliferation were assessed. Before the implantation, a surgical procedure of bilateral full-thickness uterine resection (0.5-2.0 cm long and 0.3 cm wide) was performed to obtain the rat uterine injury model, while the sham-operated rats were used as controls. Hematoxylin-eosin (H&E) staining results and fertility of female rats in each group were assessed to determine the critical resection length of the full-thickness uterine resection. Then SIS or UC-MSCs-SIS were implanted into the female rats from the uterine injury group, followed by assessments of H&E staining, the expression of ki67, α-SMA, and leukemia inhibitory factor (LIF), and fertility to determine the effectiveness of SIS and UC-MSCs-SIS on uterine injury in female rat. At 24, 48, and 72 h, the cells grew progressively on the SIS material. In the 1.5 cm and 2.0 cm groups, the pregnancy rate, proportion of the uterus supporting live embryo growth, number of live embryos, and proportion of live embryos were all significantly less than those in the 0.5 cm and sham-operated groups. In the 2.0 cm group, there was little tissue regeneration at the center of the injury and not conducive to subsequent assessment. The UC-MSCs-SIS and SIS groups were better on morphological development, cell proliferation, LIF expression, and fertility than the control group. UC-MSCs show good adhesion, growth, and proliferation on the SIS scaffold material. The optimal resection length in full-thickness uterine resection on female rat is 1.5 cm. UC-MSCs-SIS is the effective treatment for repairing a injury after the full-thickness resection of the uterus in this research. Impact Statement The acquired severe uterus injury is a serious condition, which prone to uterine adhesions. Postoperative endometrial repairment and prevention of intrauterine adhesion recurrence are two major clinical challenges. Fortunately, the development of tissue engineering technology makes repairing a uterine injury possible. There are two main contributions from this study. First, due to ethical requirements, it is difficult to assess the repairing effect on uterus by invasive experiments in a clinical practice. Therefore, we constructed a full-thickness uterine injury rat model, which allows us to assess the repairing effect of treatments after severe uterine injuries . Second, it explored the effect of using a combination of and umbilical cord mesenchymal stem cells and small intestine submucosa materials on improving uterine repairments, providing a potential possibility for a future clinical practice.

摘要

评估组织工程材料结合猪小肠黏膜下层(SIS)和脐带间充质干细胞(UC-MSCs)在全层子宫切除后雌性大鼠子宫损伤中的有效性,为临床治疗术后子宫损伤提供依据。在与 SIS 和 UC-MSCs 复杂培养后,评估细胞黏附、生长和增殖。在植入前,对大鼠进行双侧全层子宫切除术(0.5-2.0cm 长,0.3cm 宽),获得大鼠子宫损伤模型,而假手术大鼠作为对照。评估各组大鼠的苏木精-伊红(H&E)染色结果和生育能力,以确定全层子宫切除术的临界切除长度。然后将 SIS 或 UC-MSCs-SIS 植入子宫损伤组雌性大鼠,再进行 H&E 染色、ki67、α-SMA 和白血病抑制因子(LIF)表达及生育能力评估,以确定 SIS 和 UC-MSCs-SIS 对雌性大鼠子宫损伤的有效性。在 24、48 和 72 小时时,细胞逐渐在 SIS 材料上生长。在 1.5cm 和 2.0cm 组中,妊娠率、支持胚胎生长的子宫比例、活胚胎数和活胚胎比例均明显低于 0.5cm 组和假手术组。在 2.0cm 组中,损伤中心部位组织再生较少,不利于后续评估。与对照组相比,UC-MSCs-SIS 组和 SIS 组的形态发育、细胞增殖、LIF 表达和生育能力更好。UC-MSCs 在 SIS 支架材料上表现出良好的黏附、生长和增殖能力。在雌性大鼠的全层子宫切除术中,最佳切除长度为 1.5cm。UC-MSCs-SIS 是本研究中全层子宫切除术后修复损伤的有效治疗方法。

影响陈述

获得严重的子宫损伤是一种严重的情况,容易发生子宫粘连。术后子宫内膜修复和预防宫腔粘连复发是两个主要的临床挑战。幸运的是,组织工程技术的发展使得修复子宫损伤成为可能。本研究有两个主要贡献。首先,由于伦理要求,在临床实践中,通过侵入性实验评估子宫的修复效果是困难的。因此,我们构建了全层子宫损伤大鼠模型,使我们能够评估严重子宫损伤后的治疗效果。其次,它探索了使用猪小肠黏膜下层(SIS)和脐带间充质干细胞(UC-MSCs)的组合以及材料对改善子宫修复的效果,为未来的临床实践提供了一种潜在的可能性。

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