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Article

Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques

1
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 1608582, Japan
2
Department of Pathology, Shiga University of Medical Science, Shiga 5202192, Japan
3
Department of Pathology, Keio University School of Medicine, Tokyo 1608582, Japan
4
Department of Surgery, Kidney Center, Tokyo Women’s Medical University, Tokyo 1628666, Japan
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Department of Pediatric Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
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Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
7
Department of Anesthesiology, Saiseikai Kanagawaken Hospital, Kanagawa 2210821, Japan
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Research Center for Animal Life Science, Shiga University of Medical Science, Shiga 5202192, Japan
9
The Corporation for Production and Research of Laboratory Primates, Ibaraki 3050003, Japan
10
Safety Research Center, Ina Research Inc., Nagano 3994501, Japan
11
Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa 2591193, Japan
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(10), 1572; https://doi.org/10.3390/jcm8101572
Received: 31 August 2019 / Revised: 26 September 2019 / Accepted: 30 September 2019 / Published: 1 October 2019
(This article belongs to the Special Issue Uterus Transplantation)
Uterus transplantation (UTx) is an option for women with uterine factor infertility to have a child, but is still in the experimental stage. Therefore, allogeneic animal models of UTx are required for resolution of clinical issues. In this study, long-term outcomes were evaluated in four recipients (cases 1–4) after allogeneic UTx in cynomolgus macaques. Immunosuppression with antithymocyte globulin induction and a triple maintenance regimen was used. Postoperative ultrasonography and biopsy of the transplanted uterus and immunoserological examinations were performed. All four recipients survived for >3 months after surgery, but continuous menstruation did not resume, although temporary menstruation occurred (cases 1 and 2). All animals were euthanized due to irreversible rejection and no uterine blood flow (cases 1, 2 and 4) and post-transplant lymphoproliferative disorder (case 3). Donor-specific antibodies against MHC class I and II were detected in cases 1, 2 and 4, but not in case 3. Peripheral lymphocyte counts tended to elevate for CD3+, CD20+ and NK cells in conjunction with uterine rejection, and all animals had elevated stimulation indexes of mixed lymphocyte reaction after surgery. Establishment of allogeneic UTx in cynomolgus macaque requires further exploration of immunosuppression, but the clinicopathological features of uterine rejection are useful for development of human UTx. View Full-Text
Keywords: uterus transplantation; uterine transplantation; cynomolgus macaque; uterine factor infertility; allogeneic uterus transplantation; rejection uterus transplantation; uterine transplantation; cynomolgus macaque; uterine factor infertility; allogeneic uterus transplantation; rejection
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MDPI and ACS Style

Kisu, I.; Ishigaki, H.; Emoto, K.; Kato, Y.; Yamada, Y.; Matsubara, K.; Obara, H.; Masugi, Y.; Matoba, Y.; Adachi, M.; Banno, K.; Saiki, Y.; Itagaki, I.; Kawamoto, I.; Iwatani, C.; Nakagawa, T.; Tsuchiya, H.; Sasamura, T.; Urano, H.; Ema, M.; Ogasawara, K.; Aoki, D.; Nakagawa, K.; Shiina, T. Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques. J. Clin. Med. 2019, 8, 1572. https://doi.org/10.3390/jcm8101572

AMA Style

Kisu I, Ishigaki H, Emoto K, Kato Y, Yamada Y, Matsubara K, Obara H, Masugi Y, Matoba Y, Adachi M, Banno K, Saiki Y, Itagaki I, Kawamoto I, Iwatani C, Nakagawa T, Tsuchiya H, Sasamura T, Urano H, Ema M, Ogasawara K, Aoki D, Nakagawa K, Shiina T. Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques. Journal of Clinical Medicine. 2019; 8(10):1572. https://doi.org/10.3390/jcm8101572

Chicago/Turabian Style

Kisu, Iori, Hirohito Ishigaki, Katsura Emoto, Yojiro Kato, Yohei Yamada, Kentaro Matsubara, Hideaki Obara, Yohei Masugi, Yusuke Matoba, Masataka Adachi, Kouji Banno, Yoko Saiki, Iori Itagaki, Ikuo Kawamoto, Chizuru Iwatani, Takahiro Nakagawa, Hideaki Tsuchiya, Takako Sasamura, Hiroyuki Urano, Masatsugu Ema, Kazumasa Ogasawara, Daisuke Aoki, Kenshi Nakagawa, and Takashi Shiina. 2019. "Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques" Journal of Clinical Medicine 8, no. 10: 1572. https://doi.org/10.3390/jcm8101572

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