<strong>Background:</strong> Intrauterine Adhesions (IUAs) or Asherman’s Syndrome (AS) usually contains symptoms such as decreased menstrual flow or even amenorrhea, chronic pelvic pain, recurrent abortio...<strong>Background:</strong> Intrauterine Adhesions (IUAs) or Asherman’s Syndrome (AS) usually contains symptoms such as decreased menstrual flow or even amenorrhea, chronic pelvic pain, recurrent abortion and infertility. The current treatment of IUAs includes hysteroscopic adhesiolysis, oral hormone and biological barriers, but each of them has limitation. Stem cell therapy may be an expanding field seeking for therapy in IUAs. <strong>Objective: </strong>We will discuss current advances in stem cell therapy as a treatment for endometrial pathophysiology. <strong>Materials and Methods:</strong> We search on PubMed, Embase and Cochrane library and select several keywords on researches, then review the cell biology theories and animal experiments, finally do meta-analysis in human clinical trials. <strong>Results: </strong>77 articles on PubMed, 71 articles on Embase and 17 articles on Cochrane Library, as a result, 37 articles are included under the criteria, which are intrauterine adhesions (IUAs), Asherman’s Syndrome (AS), cell therapy, stem cells, bone marrow stem cells, clinical trials, recent 10 years and human or animal experiments. The included criteria: original articles, cohort study, case control study, animal experiments, human clinical trials, high quality, 10 years recent. The excluded articles are case reports, meeting reports, low quality or more than 10 years ago. <strong>Conclusion:</strong> Stem cell may be a new therapeutic schedule for IUAs in the future clinical treatment, but it is necessary to compare it with traditional therapy such as oral hormone, also the development of random clinical tests should proceed. For clinical treatment on IUAs, stem cells could be a new choice.展开更多
Asherman’s syndrome(AS),a leading cause of uterine infertility worldwide,is characterized by scarring of the uterine surfaces lacking endometrial epithelial cells,which prevents endometrial regeneration.Current resea...Asherman’s syndrome(AS),a leading cause of uterine infertility worldwide,is characterized by scarring of the uterine surfaces lacking endometrial epithelial cells,which prevents endometrial regeneration.Current research on cell therapy for AS focuses on mesenchymal and adult stem cells from the endometrium.However,insufficient number,lack of purity,and rapid senescence of endometrial epithelial progenitor cells(EEPCs)during experimental processes restrict their use in cell therapies.In this study,we induced human embryonic stem cells-9(H9-ESC)into EEPCs by optimizing the induction factors from the definitive endoderm.EEPCs,which act as endometrial epithelial cells,accompanied by human endometrial stromal cells provide a niche environment for the development of endometrial membrane organoids(EMOs)in an in vitro 3D culture model.To investigate the function of EMOs,we transplanted tissue-engineered constructs with EMOs into an in vivo rat AS model.The implantation of EMOs into the damaged endometrium facilitates endometrial regeneration and angiogenesis.Implanting EMOs developed from human embryonic stem cells into the endometrium might prove useful for“endometrial re-engineering”in the treatment of Asherman’s syndrome.展开更多
Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the...Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.展开更多
文摘<strong>Background:</strong> Intrauterine Adhesions (IUAs) or Asherman’s Syndrome (AS) usually contains symptoms such as decreased menstrual flow or even amenorrhea, chronic pelvic pain, recurrent abortion and infertility. The current treatment of IUAs includes hysteroscopic adhesiolysis, oral hormone and biological barriers, but each of them has limitation. Stem cell therapy may be an expanding field seeking for therapy in IUAs. <strong>Objective: </strong>We will discuss current advances in stem cell therapy as a treatment for endometrial pathophysiology. <strong>Materials and Methods:</strong> We search on PubMed, Embase and Cochrane library and select several keywords on researches, then review the cell biology theories and animal experiments, finally do meta-analysis in human clinical trials. <strong>Results: </strong>77 articles on PubMed, 71 articles on Embase and 17 articles on Cochrane Library, as a result, 37 articles are included under the criteria, which are intrauterine adhesions (IUAs), Asherman’s Syndrome (AS), cell therapy, stem cells, bone marrow stem cells, clinical trials, recent 10 years and human or animal experiments. The included criteria: original articles, cohort study, case control study, animal experiments, human clinical trials, high quality, 10 years recent. The excluded articles are case reports, meeting reports, low quality or more than 10 years ago. <strong>Conclusion:</strong> Stem cell may be a new therapeutic schedule for IUAs in the future clinical treatment, but it is necessary to compare it with traditional therapy such as oral hormone, also the development of random clinical tests should proceed. For clinical treatment on IUAs, stem cells could be a new choice.
基金the National Nature Science Foundation of China(grant no.81401179).
文摘Asherman’s syndrome(AS),a leading cause of uterine infertility worldwide,is characterized by scarring of the uterine surfaces lacking endometrial epithelial cells,which prevents endometrial regeneration.Current research on cell therapy for AS focuses on mesenchymal and adult stem cells from the endometrium.However,insufficient number,lack of purity,and rapid senescence of endometrial epithelial progenitor cells(EEPCs)during experimental processes restrict their use in cell therapies.In this study,we induced human embryonic stem cells-9(H9-ESC)into EEPCs by optimizing the induction factors from the definitive endoderm.EEPCs,which act as endometrial epithelial cells,accompanied by human endometrial stromal cells provide a niche environment for the development of endometrial membrane organoids(EMOs)in an in vitro 3D culture model.To investigate the function of EMOs,we transplanted tissue-engineered constructs with EMOs into an in vivo rat AS model.The implantation of EMOs into the damaged endometrium facilitates endometrial regeneration and angiogenesis.Implanting EMOs developed from human embryonic stem cells into the endometrium might prove useful for“endometrial re-engineering”in the treatment of Asherman’s syndrome.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030505)Key research and development program of Jiangsu province (BE2016612), Jiangsu Biobank of Clinical Resources (BM2015004)+1 种基金the Key Laboratory for Maternal-Fetal Medicine from the Health Department of Jiangsu Province, China (XK201102)Project of Nanjing clinical medicine center and the National Natural Science Foundation of China (81401223)
文摘Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.
