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

Cell sheet uterine transplantation regenerates endometrial tissue with both histological structure and physiological function similar to normal endometrium, restoring fertility. Endometrial cell sheet transplantation is relevant for patients with human endometrial disorders.

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Volume 110, Issue 1, Pages 172–181.e4

Authors:

Goro Kuramoto, M.D., Ph.D., Tatsuya Shimizu, M.D., Ph.D. Tatsuya Shimizu, Soichi Takagi, Ph.D., Ken Ishitani, M.D., Ph.D., Hideo Matsui, M.D., Ph.D., Teruo Okano, Ph.D.

Abstract:

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.


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Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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