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Mesenchymal stem cells and their conditioned medium can enhance the repair of uterine defects in a rat model
Authors:Chi-Hong Ho  Chen-Wei Lan  Chen-Yi Liao  Shih-Chieh Hung  Hsin-Yang Li  Yen-Jen Sung
Institution:1. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC;2. Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC;3. Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC;4. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC;5. Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
Abstract:

Background

Our aim was to examine the roles of mesenchymal stem cell (MSC) transplantation in the repair of large uterine defects.

Methods

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.

Results

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.

Conclusion

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.
Keywords:Mesenchymal stem cells  Paracrine effects  Transplantation  Uterine defect repair  Uterine surgery
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