Tissue engineered uterine tissue supports pregnancy in a rat model

Abstract

Background: Absolute uterine factor infertility affects about 1:500 women in fertile age. This can now be cured by uterus transplantation, a procedure that involves risky donor surgery and side effects of immunosuppression. The creation of a tissue-­‐engineered uterus/uterine tissue using the patient’s own stem cells would circumvent these issues. Objective: To create a tissue engineered uterine patch for repair of a partially defect uterus. Methods: Three different decellularized uterine scaffolds were recellularized in vitro with primary uterine cells and mesenchymal stem cells (MSCs). The patches were transplanted in vivo to investigate their tissue adaptation and supporting capacity during pregnancy. Recellularization efficiency and graft quality were analyzed morphologically, immunohistochemically, and by real-­‐time quantitative polymerase chain reaction (qPCR). The location and number of fetuses were documented during embryonic day 16–20. Results: 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. No placentation was formed over the patch areas in any of the experiment groups. qPCR and immunohistochemistry revealed uterus-­‐ like tissue in the patches that had been reconstructed by infiltrating host cells after transplantation. No mesenchymal stem cells remained in the grafts. Conclusions: Primary uterine cells and MSCs can be used to reconstruct decellularized uterine tissue, and the tissue engineered uterine patch can be used to support pregnancy in a partially defect uterus. The bioengineered patches made from triton-­‐X100+DMSO-­‐ generate scaffolds were supportive during pregnancy. These protocols should be explored further to develop suitable grafting material to repair a partially defect uteri and possibly to create a whole bioengineered uterus for a uterus transplantation.