Endometrial regeneration using cell sheet transplantation techniques in rats facilitates successful fertilization and pregnancy

Objective: To regenerate functional endometrium tissue using “cell sheet” techniques as a regenerative medicine approach to address endometrial disorders causing female factor infertility. Design: In vivo experimental study. Setting: Preclinical surgical and biomedical research laboratories. Animal(s): Green fluorescent protein (GFP) transgenic rats [SD-Tg (CAG-EGFP) rats] and nude rats (F344/NJcl-rnu/rnu). Intervention(s): GFP-positive rat uterine-derived cells as cell sheets were transplanted into resected rat uterine endometrial sites. Transplanted cell sheet areas were then analyzed using macroscopic observations and histological analysis including immunohistochemistry. Subsequently, crossbreeding was performed to establish fertility and confirm pregnancy in the rat-regenerated uterus. Main Outcome Measure(s): Morphologic and biochemical markers of regenerated endometrium and establishment of pregnancy in otherwise sterile animals. Result(s): After cell sheet transplantation, regenerated endometrium was confirmed as GFP-positive tissue engraftment both visually and under histological analysis. After crossbreeding, GFP-positive tissue areas and living fetuses were observed in the transplantation group. Conclusion(s): Cell sheet transplantation can regenerate endometrial tissue with histological structure and physiological function supporting pregnancy similar to normal endometrial tissue. Translation of this endometrial cell sheet transplantation method to human patients with endometrial disorders could yield a novel therapy for uterine infertility.