title: Amniotic fluid stem cells prevent follicle atresia and rescue fertility of mice with premature ovarian failure induced by chemotherapy.
abstract: Chemotherapy used to treat cancer may cause irreversible premature ovarian failure (POF). Of late, amniotic fluid stem cells (AFSCs) provide a novel source for regenerative medicine because of their primitive stage, low immunogenicity, and easy accessibility. In this study, we isolated AFSCs from transgenic mice that ubiquitously express enhanced green fluorescence protein (EGFP). These AFSCs exhibited morphologies, immunophenotypes, and mesoderm trilineage differentiation potentials similar to mesenchymal stem cells (MSCs). Further, AFSCs proliferated faster than MSCs and expressed OCT4, a marker for pluripotency. To investigate their potential in recovering fertility in POF model, AFSCs were transplanted into the ovaries of mice with POF six weeks post induction using chemotherapeutic drugs, busulfan and cyclophosphamide. AFSCs could rescue the reproductive ability of mice with POF by preventing follicle atresia and sustaining the healthy follicles. Notably, the transplanted AFSCs did not differentiate into granulosa and germline cells in vivo. After one month, the decreased numbers of transplanted AFSCs accompanied with the reduced beneficial effects indicated that the therapeutic efficacy were directly from AFSCs. These findings demonstrated the therapeutic effects of AFSCs and suggested the promise of AFSCs for treating infertility and POF caused by chemotherapy.
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Guan-Yu
authors.initials: GY
authors.lastname: Xiao
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Liu
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Chun-Chun
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Yen-Hua
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan; Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.
authors.forename: Winston Teng-Kuei
authors.initials: WT
authors.lastname: Cheng
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Shinn-Chih
authors.initials: SC
authors.lastname: Wu
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005298:Fertility; D005434:Flow Cytometry; D005496:Follicular Atresia; D051379:Mice; D008822:Mice, Transgenic; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers