title: Preventive effect of oral mucosal epithelial cell sheets on intrauterine adhesions.
abstract: OBJECTIVE
  Can regenerative-medicine techniques using oral mucosal epithelial cell sheets (OMECS) provide a new treatment method for intrauterine adhesions (IUA) which cause female infertility?
  
  
  CONCLUSIONS
  Transplantation of OMECS was confirmed to be effective in preventing IUA after endometrial damage in rats.
  
  
  BACKGROUND
  Uterine disorders such as IUA, commonly known as Asherman's syndrome, are one factor that can result in infertility. Clinical therapy for this kind of disease is targeted at the prevention of re-adhesion by surgical synechiotomy, administration of hormones after the operation, and the use of intrauterine devices. Recently, a new approach called 'cell-sheet engineering', which harvests confluent culture cells as a contiguous cell sheet having intact cell-cell junctions and an extracellular matrix, without having to use enzymatic treatment, has been developed for tissue regeneration.
  
  
  METHODS
  OMECS were prepared from rat oral mucosal tissues. An IUA model was made in rat uteri, and OMECS were transplanted into the model. Uteri transplanted with OMECS were compared with the non-transplanted control uteri by histological analysis at 1, 2 and 8 days after surgery (n = 3).
  
  
  METHODS
  Oral mucosal tissues were resected from neonatal rats, and oral mucosal epithelial cells were collected with enzymatic treatment. An isolated cell suspension was seeded on a temperature-responsive cell culture-insert and incubated. After being detached from the insert, a cell sheet was transplanted onto the endometrium defect. At 1, 2 and 8 days after surgery, uteri were resected and examined.
  
  
  RESULTS
  Histological examination of the non-treated specimens at 1, 2 and 8 days after surgery did not show any uterine cavities typically caused by IUA. In contrast, the histology of uteri transplanted with OMECS immediately after endometrial damage showed the presence of uterine cavities, and furthermore, stratified squamous epithelial cells on the luminal surface (n = 3).
  
  
  CONCLUSIONS
  The results of this study are difficult to apply directly to humans, because the structure and function of rat uteri are different from those of human.
  
  
  CONCLUSIONS
  Transplantation of OMECS offers a reliable method not only to protect the woman's fertility from intrauterine re-adhesion after synechiotomy for IUA or uterine lumen adhesion but also to prevent adhesion after any intrauterine surgery in clinical cases.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Kuramoto
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Takagi
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishitani
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan shimizu.tatsuya@twmu.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsui
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006175:Gynatresia / Q000601:surgery / Q000628:therapy*; D007150:Immunohistochemistry; D009061:Mouth Mucosa / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration; D011916:Rats, Inbred F344; D011923:Rats, Nude; D055647:Rats, Transgenic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D000267:Tissue Adhesions / Q000601:surgery / Q000628:therapy*; D023822:Tissue Engineering; D014599:Uterus / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D015415:Biomarkers; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins
keywords: Asherman's syndrome; cell sheet; intrauterine adhesions; regenerative medicine; tissue engineering