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Open AccessArticle

First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques

1
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 1608582, Japan
2
Department of Surgery, Division of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo 1428555, Japan
3
Department of Pathology, Keio University School of Medicine, Tokyo 1608582, Japan
4
Department of Pathology, Shiga University of Medical Science, Shiga 5202192, Japan
5
Department of Pediatric Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
6
Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
7
Department of Anesthesiology, Saiseikai Kanagawaken Hospital, Kanagawa 2210821, Japan
8
Research Center for Animal Life Science, Shiga University of Medical Science, Shiga 5202192, Japan
9
Safety Research Center, Ina Research Inc., Nagano 3994501, Japan
10
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. 2020, 9(11), 3694; https://doi.org/10.3390/jcm9113694
Received: 27 September 2020 / Revised: 2 November 2020 / Accepted: 3 November 2020 / Published: 17 November 2020
(This article belongs to the Special Issue Uterus Transplantation)
Delivery following uterus transplantation (UTx)—an approach for treating uterine factor infertility—has not been reported in nonhuman primate models. Here, six female major histocompatibility complex (MHC)-defined cynomolgus macaques that underwent allogeneic UTx were evaluated. Antithymocyte globulin and rituximab were administered to induce immunosuppression and a triple maintenance regimen was used. Menstruation resumed in all animals with long-term survival, except one, which was euthanized due to infusion associated adverse reaction to antithymocyte globulin. Donor-specific antibodies (DSA) were detected in cases 2, 4, and 5, while humoral rejection occurred in cases 4 and 5. Post-transplant lymphoproliferative disorder (PTLD) developed in cases 2 and 3. Pregnancy was attempted in cases 1, 2, and 3 but was achieved only in case 2, which had haploidentical donor and recipient MHCs. Pregnancy was achieved in case 2 after recovery from graft rejection coincident with DSA and PTLD. A cesarean section was performed at full-term. This is the first report of a successful livebirth following allogeneic UTx in nonhuman primates, although the delivery was achieved via UTx between a pair carrying haploidentical MHCs. Experimental data from nonhuman primates may provide important scientific knowledge needed to resolve unsolved clinical issues in UTx. View Full-Text
Keywords: allogeneic uterus transplantation; cynomolgus macaque; donor specific antibody; humoral rejection; post-transplant lymphoproliferative disorder; uterine transplantation; uterine factor infertility; uterus transplantation allogeneic uterus transplantation; cynomolgus macaque; donor specific antibody; humoral rejection; post-transplant lymphoproliferative disorder; uterine transplantation; uterine factor infertility; uterus transplantation
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MDPI and ACS Style

Kisu, I.; Kato, Y.; Masugi, Y.; Ishigaki, H.; Yamada, Y.; Matsubara, K.; Obara, H.; Emoto, K.; Matoba, Y.; Adachi, M.; Banno, K.; Saiki, Y.; Sasamura, T.; Itagaki, I.; Kawamoto, I.; Iwatani, C.; Nakagawa, T.; Murase, M.; Tsuchiya, H.; Urano, H.; Ema, M.; Ogasawara, K.; Aoki, D.; Nakagawa, K.; Shiina, T. First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques. J. Clin. Med. 2020, 9, 3694. https://doi.org/10.3390/jcm9113694

AMA Style

Kisu I, Kato Y, Masugi Y, Ishigaki H, Yamada Y, Matsubara K, Obara H, Emoto K, Matoba Y, Adachi M, Banno K, Saiki Y, Sasamura T, Itagaki I, Kawamoto I, Iwatani C, Nakagawa T, Murase M, Tsuchiya H, Urano H, Ema M, Ogasawara K, Aoki D, Nakagawa K, Shiina T. First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques. Journal of Clinical Medicine. 2020; 9(11):3694. https://doi.org/10.3390/jcm9113694

Chicago/Turabian Style

Kisu, Iori; Kato, Yojiro; Masugi, Yohei; Ishigaki, Hirohito; Yamada, Yohei; Matsubara, Kentaro; Obara, Hideaki; Emoto, Katsura; Matoba, Yusuke; Adachi, Masataka; Banno, Kouji; Saiki, Yoko; Sasamura, Takako; Itagaki, Iori; Kawamoto, Ikuo; Iwatani, Chizuru; Nakagawa, Takahiro; Murase, Mitsuru; Tsuchiya, Hideaki; Urano, Hiroyuki; Ema, Masatsugu; Ogasawara, Kazumasa; Aoki, Daisuke; Nakagawa, Kenshi; Shiina, Takashi. 2020. "First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques" J. Clin. Med. 9, no. 11: 3694. https://doi.org/10.3390/jcm9113694

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