title: Bioengineered uterine tissue supports pregnancy in a rat model.
abstract: To create a bioengineered uterine patch for uterine repair of a partially defect uterus.
  
  
  
  Three different decellularized uterine scaffolds were recellularized in vitro with primary uterine cells and green fluorescent protein- (GPF-) labeled bone marrow-derived mesenchymal stem cells (GFP-MSCs). The patches were transplanted in vivo to investigate their tissue adaptation and supporting capacity during pregnancy.
  
  
  
  Research laboratory.
  
  
  
  Female Lewis rats (n = 9) as donors to generate whole-uterus scaffolds using three different protocols (n = 3 per protocol); Sprague Dawley rats (n = 40) for primary uterus cell isolation procedures (n = 10) and for transplantation/pregnancy studies (n = 30); and male Sprague Dawley rats (n = 12) for mating.
  
  
  
  Decellularization was achieved by whole-uterus perfusion with buffered or nonbuffered Triton-X100 and dimethyl sulfoxide (DMSO; group P1/P2) or with sodium deoxycholate (group P3). Primary uterine cells and GFP-MSCs were used to develop uterine tissue constructs, which were grafted to uteri with partial tissue defects.
  
  
  
  Recellularization efficiency and graft quality were analyzed morphologically, immunohistochemically, and by real-time quantitative polymerase chain reaction (PCR). The location and number of fetuses were documented during pregnancy days 16-20.
  
  
  
  Pregnancy and fetal development were normal in groups P1 and P2, with fetal development over patched areas. Group P3 showed significant reduction of fetal numbers, and embryos were not seen in the grafted area. Quantitative PCR and immunohistochemistry revealed uterus-like tissue in the patches, which had been further reconstructed by infiltrating host cells after transplantation.
  
  
  
  Primary uterine cells and MSCs can be used to reconstruct decellularized uterine tissue. The bioengineered patches made from triton-X100+DMSO-generated scaffolds were supportive during pregnancy. These protocols should be explored further to develop suitable grafting material to repair partially defect uteri and possibly to create a complete bioengineered uterus.
authors.affiliation: Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: mats.hellstrom@gu.se.
authors.forename: Mats
authors.initials: M
authors.lastname: Hellström
authors.affiliation: Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Moreno-Moya
authors.affiliation: Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Bandstein
authors.affiliation: Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Bom
authors.affiliation: Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Randa R
authors.initials: RR
authors.lastname: Akouri
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Brännström
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005865:Gestational Age; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008098:Litter Size; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011917:Rats, Inbred Lew; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014162:Transfection; D014599:Uterus / Q000378:metabolism / Q000637:transplantation*
chemical_list: D012333:RNA, Messenger; D049452:Green Fluorescent Proteins
keywords: Decellularization; in vivo; recellularization; tissue engineering; uterus