title: Mesenchymal stem cell-derived angiogenin promotes primodial follicle survival and angiogenesis in transplanted human ovarian tissue.
abstract: BACKGROUND
  We have recently reported that human bone marrow-derived mesenchymal stem cells (MSCs) facilitate angiogenesis and prevent follicle loss in xenografted human ovarian tissues. However, the mechanism underlying this effect remains to be elucidated. Thus, determining the paracrine profiles and identifying the key secreted factors in MSCs co-transplanted with ovarian grafts are essential for the future application of MSCs.
  
  
  METHODS
  In this study, we used cytokine microarrays to identify differentially expressed proteins associated with angiogenesis in frozen-thawed ovarian tissues co-transplanted with MSCs. The function of specific secreted factors in MSCs co-transplanted with human ovarian tissues was studied via targeted blockade with short-hairpin RNAi and the use of monoclonal neutralizing antibodies.
  
  
  RESULTS
  Our results showed that angiogenin (ANG) was one of the most robustly up-regulated proteins (among 42 protein we screened, 37 proteins were up-regulated). Notably, the targeted depletion of ANG with short-hairpin RNAi (shANG) or the addition of anti-ANG monoclonal neutralizing antibodies (ANG Ab) significantly reversed the MSC-stimulated angiogenesis, increased follicle numbers and protective effect on follicle apoptosis.
  
  
  CONCLUSIONS
  Our results indicate that ANG plays a critical role in regulating angiogenesis and follicle survival in xenografted human ovarian tissues. Our findings provide important insights into the molecular mechanism by which MSCs promote angiogenesis and follicle survival in transplanted ovarian tissues, thus providing a theoretical basis for their further application.
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.|Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Shenzhen Hospital, No.1120 Lotus Road, FuTian District, Shenzhen, Guangdong, 518000, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Cuilin
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.|Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, 100004, China.
authors.forename: Tianren
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Tailang
authors.initials: T
authors.lastname: Yin
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, V5Z4H4, Canada.
authors.forename: Hsun-Ming
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China. jie.qiao@263.net.|Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China. jie.qiao@263.net.|Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China. jie.qiao@263.net.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006080:Ovarian Follicle / Q000098:blood supply* / Q000254:growth & development / Q000637:transplantation; D010052:Ovariectomy; D034622:RNA Interference; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D057134:Antibodies, Neutralizing; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: Angiogenin; Fertility preservation; Follicle survival; Mesenchymal stem cell; Ovarian tissue transplantation