First successful delivery after uterus transplantation in mhc-defined cynomolgus macaques

Iori Kisu, Yojiro Kato, Yohei Masugi, Hirohito Ishigaki, Yohei Yamada, Kentaro Matsubara, Hideaki Obara, Katsura Emoto, Yusuke Matoba, Masataka Adachi, Kouji Banno, Yoko Saiki, Takako Sasamura, Iori Itagaki, Ikuo Kawamoto, Chizuru Iwatani, Takahiro Nakagawa, Mitsuru Murase, Hideaki Tsuchiya, Hiroyuki UranoMasatsugu Ema, Kazumasa Ogasawara, Daisuke Aoki, Kenshi Nakagawa, Takashi Shiina

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number3694
Pages (from-to)1-23
Number of pages23
JournalJournal of Clinical Medicine
Volume9
Issue number11
DOIs
Publication statusPublished - 2020 Nov

Keywords

  • Allogeneic uterus transplantation
  • Cynomolgus macaque
  • Donor specific antibody
  • Humoral rejection
  • Post-transplant lymphoproliferative disorder
  • Uterine factor infertility
  • Uterine transplantation
  • Uterus transplantation

ASJC Scopus subject areas

  • Medicine(all)

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