title: FTY720 and cyclosporin protect ovarian tissue grafted into rabbits.
abstract: OBJECTIVE
  To determine whether FTY720 combined with CsA has immunomodulatory effects on human ovarian tissue transplanted to the back muscle of rabbits for an 8-week period.
  
  
  METHODS
  We selected rabbits as recipients of ovarian xenografts with and without treatment by CsA and FTY720. Ovarian fragments from twelve patients were cut into 2 mm × 2 mm, 1-2mm thick pieces and randomly distributed into four groups: Group 1 (FTY720 2 mg/kg/d+CsA 3 mg/kg/d), Group 2 (FTY720 1 mg/kg/d+CsA 3mg/kg/d), Group 3 (FTY720 0.5 mg/kg/d+CsA 3mg/kg/d) and Group 4 for control (CsA 3 mg/kg/d). FTY720 was started three days before transplantation and was given daily after transplantation. CsA was administrated post-transplantation. All the animals were killed 8 weeks post- transplantation. Levels of serum estrogen (E2), interferon-γ (IFN-γ) and interleukin-4 (IL-4) were detected by radioimmunoassay and ELISA. Anti-CD31 and anti-Ki-67 antibodies were used to evaluate neo-vascularization in xenografts and proliferation activity of ovarian follicles. Peripheral CD4+/CD8+ T cells were analyzed by flow cytometry.
  
  
  RESULTS
  Combined treatment with cyclosporin A and FTY720 improved graft survival and reduced peripheral CD4+ and CD8+ T cell counts compared to treatment with cyclosporin A alone. Neovascularization took place in the peripheral zone of the xenograft while granulosa cells, positively stained by Ki-67, were found in early-stage follicles and stromal cells in the combined treatment groups.
  
  
  CONCLUSIONS
  FTY720 in combination with cyclosporin A maintains human ovarian xenografts in these rabbit models.
authors.affiliation: Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang Province, China.
authors.forename: Yingfen
authors.initials: Y
authors.lastname: Ying
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Yaxia
authors.initials: Y
authors.lastname: Chen
authors.forename: Jingyi
authors.initials: J
authors.lastname: Jiang
authors.forename: Yinluan
authors.initials: Y
authors.lastname: Ouyang
authors.forename: Hefeng
authors.initials: H
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D019394:Ki-67 Antigen / Q000096:biosynthesis; D010053:Ovary / Q000637:transplantation*; D011409:Propylene Glycols / Q000627:therapeutic use*; D011817:Rabbits; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014183:Transplantation, Heterologous
chemical_list: D019394:Ki-67 Antigen; D011409:Propylene Glycols; D015847:Interleukin-4; D007371:Interferon-gamma; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: FTY720; Immune regulation; Ki-67; Ovarian tissue; Xenotransplantation