title: Human endometrial mesenchymal stem cells restore ovarian function through improving the renewal of germline stem cells in a mouse model of premature ovarian failure.
abstract: BACKGROUND
  Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood have mesenchymal stem/stromal cells (MSCs) characteristics and can differentiate into cell types that arise from all three germ layers. We hypothesized that EnSCs may offer promise for restoration of ovarian dysfunction associated with premature ovarian failure/insufficiency (POF/POI).
  
  
  METHODS
  Mouse ovaries were injured with busulfan and cyclophosphamide (B/C) to create a damaged ovary mouse model. Transplanted EnSCs were injected into the tail vein of sterilized mice (Chemoablated with EnSCs group; n = 80), or culture medium was injected into the sterilized mice via the tail vein as chemoablated group (n = 80). Non-sterilized mice were untreated controls (n = 80). Overall ovarian function was measured using vaginal smears, live imaging, mating trials and immunohistochemical techniques.
  
  
  RESULTS
  EnSCs transplantation increased body weight and improved estrous cyclicity as well as restored fertility in sterilized mice. Migration and localization of GFP-labeled EnSCs as measured by live imaging and immunofluorescent methods indicated that GFP-labeled cells were undetectable 48 h after cell transplantation, but were later detected in and localized to the ovarian stroma. 5'-bromodeoxyuridine (BrdU) and mouse vasa homologue (MVH) protein double-positive cells were immunohistochemically detected in mouse ovaries, and EnSC transplantation reduced depletion of the germline stem cell (GSCs) pool induced by chemotherapy.
  
  
  CONCLUSIONS
  EnSCs derived from menstrual blood, as autologous stem cells, may restore damaged ovarian function and offer a suitable clinical strategy for regenerative medicine.
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China. laidongmei@hotmail.com.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lai
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China. wangfy@hotmail.com.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Wang
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China. yaoxf89@126.com.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Yao
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China. 10111010022@fudan.edu.cn.
authors.forename: Qiuwan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. wuxx@163.com.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. cxiang@zju.edu.cn.
authors.forename: Charlie
authors.initials: C
authors.lastname: Xiang
mesh_terms: D000328:Adult; D000818:Animals; D001835:Body Weight; D002066:Busulfan / Q000737:chemistry; D002454:Cell Differentiation; D003520:Cyclophosphamide / Q000737:chemistry; D004195:Disease Models, Animal; D004717:Endometrium / Q000473:pathology*; D030762:Estrous Cycle; D005260:Female; D005434:Flow Cytometry; D006107:Granulosa Cells / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010053:Ovary / Q000502:physiology*; D016649:Primary Ovarian Insufficiency / Q000378:metabolism* / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
chemical_list: D049452:Green Fluorescent Proteins; D003520:Cyclophosphamide; D002066:Busulfan