| Objective: Intrauterine adhesions(IUA)is a gynecological disorder characterized by menstrual disorders and conception difficulties.In recent years,the incidence of intrauterine adhesions also presrnted an upward trend,affecting the fertility of women.Studies have shown that the formation of intrauterine adhesions is directly related to the damage of endometrial basal layer of endometrial stem cells.Therefore,endometrial traumatic diseases such as intrauterine adhesions are also considered as diseases related to lack of stem cells or dysfunction.With the development of regenerative medicine and tissue engineering,stem cell transplantation therapy is gradually applied in clinic and has good therapeutic prospect.Menstrual blood stem cells(Men SCs)are the endometrial stem cells extracted from the menstrual blood discharged from the human body.The process of obtaining stem cells is highly efficient and noninvasive and shows extremely strong proliferative capacity under in vitro culture conditions.More and more research results prove that Men SCs have an excellent therapeutic effect on damaging diseases and are emerging therapeutic stem cells.Our previous experiments have shown that Men SCs can colonize the wounded rat uterus and promote the recovery of uterine morphology in rats with uterine adhesions.In this study,we plan to transplanted Men SCs into the uterine cavity by means of sub-uterine injection and to explore the possible mechanism of the therapeutic effect of Men SCs.Methods: The rat endometrium injury-intrauterine adhesions model was established by mechanical curettage.Two rat physiological cycles later,logarithmic growth phase of Men SCs or same volume of saline were injected into injured uterus.General fluorescence imaging and uterine section of the uterus Immunofluorescence staining,immunofluorescence,real-time fluorescence quantitative PCR and multifactorial test were used to evaluate the therapeutic effect of Men SCs on intrauterine adhesions model.After four cycles of treatment,effects of fertility were also evaluated.Results: MenSCs exhibit the characteristics of mesenchymal stem cells and express the pre-vascular cell markers PDGFR,CD146 and SUSD2 as well as the endometrial cell marker protein(Vimentin).2.Cell tracing with fluorescently labele revealed that Men SCs survived in the rat uterus and tended to migrate to the impaired endometrial area and colonized around the glands.3.Stem cell transplantation can significantly increase the number of uterine glands and intrauterine adhesions in rats increased tissue proliferation rate,reduce the degree of endometrial fibrosis and promote uterine wave protein(Vimentin)and cytokeratin(CK18)expression,Reduce the expression of Collagen 1.Realtime-PCR and multivariate test showed that the expression of IL1-?,IL-4 and IL-10 in uterus of uterine cavity adhesion rats were increased and the expression of IL6 and CTGF were decreased.Pregnancy test results show that after receiving stem cell transplantation,intrauterine adhesions rat embryos and live fetus were significantly higher than the placebo group.Conclusion: Men SCs can colonize the uterine endometrium of uterine cavity adhesion rats and have the chemotaxis of injury,which can increase the proliferation rate of endometrial cells and promote the growth of glandular cells and endometrium.After receiving menstrual stem cells,uterine fibrosis in rats with intrauterine adhesions was significantly reduced,endometrial stem cells related indicators increased expression of inflammatory state was inhibited.In addition,Men SCs transplantation can improve the pregnancy rate and live fetus rate in rats,significantly improve the outcome of pregnancy in IUA rats.In summary,Men SCs can improve and treat rat uterine adhesions,which has broad application prospects.The results of this study provide a theoretical basis for the clinical application of hematopoietic stem cells in the treatment of intrauterine adhesions and other endometrial lesions. |
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