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
<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) 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
Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe in...Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively safe.展开更多
Transcervical resection of adhesion(TCRA)is the standard treatment for the intrauterine adhesions,but the recurrence of adhesions is a tough problem for the gynecologist.In addition,the therapeutic strategy after TCRA...Transcervical resection of adhesion(TCRA)is the standard treatment for the intrauterine adhesions,but the recurrence of adhesions is a tough problem for the gynecologist.In addition,the therapeutic strategy after TCRA about prevention of recurrence remains controversial especially for the patients with moderate to severe intrauterine adhesions(IUAs).Hence,we designed this study to explore the safety and efficacy of fresh amnion grafts for preventing the recurrence after TCRA for patients with moderate to severe IUAs.One hundred patients with moderate to severe IUAs who presented with a history of hypomenorrhea,amenorrhea and infertility were included in the study from January 2015 to December 2017.Patients were divided into amnion group(52 patients)and chitosan group(48 patients).Fresh amnion grafts or intrauterine injections of chitosan were administered after TCRA.Transvaginal ultrasonography(TVUS)and hysteroscopy were performed at the first and third month after the operation.The surgical procedures for all patients were completed successfully without relevant complications.In amnion group,8 patients exhibited relapse in the first month and 2 patients in three months after surgery;in chitosan group,23 women exhibited relapse in the first month and 18 patients in three months after surgery.Statistical analysis revealed that the recurrence rate of adhesion in amnion group was significantly lower than those of chitosan group in the first and three months after surgery(P1=0.000,P2=0.000).After TCRA,fresh amnion graft plays a significant role in preventing further adhesions than injections of chitosan.展开更多
Asherman’s syndrome(AS)is an endometrial disorder in which intrauterine adhesions crowd the uterine cavity and wall.The fibrotic adhesions are primarily the result of invasive uterine procedures that usually involve ...Asherman’s syndrome(AS)is an endometrial disorder in which intrauterine adhesions crowd the uterine cavity and wall.The fibrotic adhesions are primarily the result of invasive uterine procedures that usually involve the insertion of surgical equipment into the uterus.This syndrome is accompanied by a number of clinical manifestations,including irregular or painful menstruation and infertility.The most prevalent treatment is hysteroscopy,which involves the physical removal of the fibrous strands.Within the last decade,however,the field has been exploring the use of cellbased therapeutics,in conjunction with biomaterials,to treat AS.This review is a recapitulation of the literature focused on cellular therapies for treating AS.展开更多
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.
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.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16040302,XDA01030505)the National Natural Science Foundation of China(81971336)+1 种基金Jiangsu Provincial Key Medical Center(YXZXB2016004)Jiangsu Provincial Obstetrics and Gynecology Innovation Center(CXZX202229)。
文摘Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively safe.
基金we appreciate Shanbi Zhou for providing the way about how to prepare the fresh amnion.And the study was funded by the Medical Research Project of Chongqing(NO.20141014)the Medical Characteristic Professional Subjects Construction Project of Chongqing(NO.2013-46).
文摘Transcervical resection of adhesion(TCRA)is the standard treatment for the intrauterine adhesions,but the recurrence of adhesions is a tough problem for the gynecologist.In addition,the therapeutic strategy after TCRA about prevention of recurrence remains controversial especially for the patients with moderate to severe intrauterine adhesions(IUAs).Hence,we designed this study to explore the safety and efficacy of fresh amnion grafts for preventing the recurrence after TCRA for patients with moderate to severe IUAs.One hundred patients with moderate to severe IUAs who presented with a history of hypomenorrhea,amenorrhea and infertility were included in the study from January 2015 to December 2017.Patients were divided into amnion group(52 patients)and chitosan group(48 patients).Fresh amnion grafts or intrauterine injections of chitosan were administered after TCRA.Transvaginal ultrasonography(TVUS)and hysteroscopy were performed at the first and third month after the operation.The surgical procedures for all patients were completed successfully without relevant complications.In amnion group,8 patients exhibited relapse in the first month and 2 patients in three months after surgery;in chitosan group,23 women exhibited relapse in the first month and 18 patients in three months after surgery.Statistical analysis revealed that the recurrence rate of adhesion in amnion group was significantly lower than those of chitosan group in the first and three months after surgery(P1=0.000,P2=0.000).After TCRA,fresh amnion graft plays a significant role in preventing further adhesions than injections of chitosan.
基金the National Institutes of Health(R01HL123920 and R01HL137093 to K.C.).Final grammatical edits were made by Jhon Cores,PhD.
文摘Asherman’s syndrome(AS)is an endometrial disorder in which intrauterine adhesions crowd the uterine cavity and wall.The fibrotic adhesions are primarily the result of invasive uterine procedures that usually involve the insertion of surgical equipment into the uterus.This syndrome is accompanied by a number of clinical manifestations,including irregular or painful menstruation and infertility.The most prevalent treatment is hysteroscopy,which involves the physical removal of the fibrous strands.Within the last decade,however,the field has been exploring the use of cellbased therapeutics,in conjunction with biomaterials,to treat AS.This review is a recapitulation of the literature focused on cellular therapies for treating AS.
