Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2018 Mar;81(3):268-276. doi: 10.1016/j.jcma.2017.03.013. Epub 2017 Sep 4.
Our aim was to examine the roles of mesenchymal stem cell (MSC) transplantation in the repair of large uterine defects.
Uterine defects were created in both uterine horns of female rats by a punch instrument, and bone marrow-derived MSCs, MSC-conditioned medium (MSC-CM) or vehicle were injected into the myometrium around the defect. The rate of uterine defect repair was monitored on day 2 and 4 after operation. Cytokine array of MSC-CM was performed, followed by neutralizing antibody experiments to clarify the exact cytokine participating in the MSC-CM-enhanced wound repair.
Transplantation of MSCs, but not myometrial cells, significantly enhanced uterine defect repair. The transplanted MSCs were detected in the uterine horn with no signs of rejection on day 4 after transplantation, when the MSC-transplanted uterine wound was nearly healed. Moreover, uterine defect repair was also accelerated by injection of MSC-CM, indicating the paracrine effects of MSCs on uterine wound healing. Cytokine array analysis further revealed that MSC-CM contained abundant cytokines and chemokines, among which high levels of interleukin-6 (IL-6) were found. Additionally, antibodies against IL-6 were shown to block MSC-CM-enhanced uterine defect repair.
This study demonstrated that transplantation of MSCs could enhance uterine defect repair by paracrine effects involving IL-6, which are findings that may be applied to facilitate uterine wound healing in the removal of huge intramural masses.
我们的目的是研究间充质干细胞(MSC)移植在修复大的子宫缺陷中的作用。
通过打孔器械在雌性大鼠的两个子宫角上造成子宫缺陷,将骨髓来源的 MSC、MSC 条件培养基(MSC-CM)或载体注射到缺陷周围的子宫肌层。在手术后第 2 天和第 4 天监测子宫缺陷的修复率。对 MSC-CM 进行细胞因子分析,然后进行中和抗体实验,以阐明确切参与 MSC-CM 增强伤口修复的细胞因子。
移植 MSC 而不是子宫细胞可显著增强子宫缺陷的修复。移植后第 4 天,移植的 MSC 被检测到在子宫角中,没有排斥迹象,此时 MSC 移植的子宫伤口几乎愈合。此外,注射 MSC-CM 也加速了子宫缺陷的修复,表明 MSC 的旁分泌作用对子宫伤口愈合的影响。细胞因子分析进一步表明,MSC-CM 含有丰富的细胞因子和趋化因子,其中白细胞介素 6(IL-6)水平较高。此外,抗 IL-6 抗体被证明可以阻断 MSC-CM 增强的子宫缺陷修复。
这项研究表明,MSC 的移植可以通过涉及 IL-6 的旁分泌作用增强子宫缺陷的修复,这一发现可能有助于在切除巨大的子宫内肿块时促进子宫伤口愈合。