Preclinical report on allogeneic uterus transplantation in non-human primates

L. Johannesson, A. Enskog, J. Mölne, C. Diaz-Garcia, A. Hanafy, P. Dahm-Kähler, Akin Tekin, P. Tryphonopoulos, P. Morales, K. Rivas, Phillip Ruiz, A. Tzakis, M. Olausson, M. Brännström

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Study Question is it possible to perform allogeneic uterus transplantation (UTx) with a donation from a live donor in a non-human primate species and what immunosuppression is needed to prevent rejection? Summary Answer Allogeneic UTx in the baboon is a donor-and recipient-safe surgical procedure; immunosuppression with induction therapy and a triple protocol should be used. What is Known Already UTx may become a treatment for absolute uterine factor infertility. Autologous UTx models have been developed in non-human primates with reports on long-term survival of the uterine grafts. Study Design, Sizeand DurationThis experimental study included 18 female baboons as uterus donors and 18 female baboons as uterus recipients. The follow-up time was 5-8 weeks. Participants/Materials, Settingand Methods Uterus retrieval was performed with extended hysterectomy including bilateral uterine and internal iliac arteries and ovarian veins. After UTx, with vascular anastomoses unilateral to the internal iliac artery and the external iliac vein, the uterus recipients received one of the following: no immunosuppression (n = 4); monotherapy (oral slow release tacrolimus) (n = 4) or induction therapy (antithymocyte globulin) followed by triple therapy (tacrolimus, mycophenolate, corticosteroids; n = 10). Surgical parameters, survival, immunosuppression and rejection patterns were evaluated. Main Results AND THE ROLE OF CHANCEThe durations of uterus retrieval and recipient surgery were around 3 and 3.5 h, respectively. The total ischemic time was around 3 h. All the recipients and the donors survived the surgery. All the recipients presented rejection to some extent within the first weeks following UTx. In one recipient, the uterus was of normal appearance at the end of the study period. In spite of occasional high (>60 ng/ml) blood levels of tacrolimus, there was no evidence of nephrotoxicity. Limitations and Reasons for CautionThis initial non-human primate allogeneic UTx study indicates that further research is needed to optimize immunosuppression protocols in order to avoid uterine rejection. Wider Implications of the Findings The findings suggest that allogeneic UTx in primate species is feasible but continued work on this issue is needed. Study Funding/Competing Interest (S)The study was funded by the Swedish Research Council, ALF University of Gothenburg, Hjalmar Svensson Foundation and by Jane and Dan Olsson Research Foundation. The authors do not have any competing interest.

Original languageEnglish
Pages (from-to)189-198
Number of pages10
JournalHuman Reproduction
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Homologous Transplantation
Primates
Uterus
Immunosuppression
Papio
Tacrolimus
Iliac Artery
Research
Iliac Vein
Antilymphocyte Serum
Graft Survival
Therapeutics
Hysterectomy
Infertility
Blood Vessels
Veins
Adrenal Cortex Hormones

Keywords

  • allogeneic
  • immunosuppression
  • rejection
  • transplantation
  • uterus

ASJC Scopus subject areas

  • Rehabilitation
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Johannesson, L., Enskog, A., Mölne, J., Diaz-Garcia, C., Hanafy, A., Dahm-Kähler, P., ... Brännström, M. (2013). Preclinical report on allogeneic uterus transplantation in non-human primates. Human Reproduction, 28(1), 189-198. https://doi.org/10.1093/humrep/des381

Preclinical report on allogeneic uterus transplantation in non-human primates. / Johannesson, L.; Enskog, A.; Mölne, J.; Diaz-Garcia, C.; Hanafy, A.; Dahm-Kähler, P.; Tekin, Akin; Tryphonopoulos, P.; Morales, P.; Rivas, K.; Ruiz, Phillip; Tzakis, A.; Olausson, M.; Brännström, M.

In: Human Reproduction, Vol. 28, No. 1, 01.01.2013, p. 189-198.

Research output: Contribution to journalArticle

Johannesson, L, Enskog, A, Mölne, J, Diaz-Garcia, C, Hanafy, A, Dahm-Kähler, P, Tekin, A, Tryphonopoulos, P, Morales, P, Rivas, K, Ruiz, P, Tzakis, A, Olausson, M & Brännström, M 2013, 'Preclinical report on allogeneic uterus transplantation in non-human primates', Human Reproduction, vol. 28, no. 1, pp. 189-198. https://doi.org/10.1093/humrep/des381
Johannesson L, Enskog A, Mölne J, Diaz-Garcia C, Hanafy A, Dahm-Kähler P et al. Preclinical report on allogeneic uterus transplantation in non-human primates. Human Reproduction. 2013 Jan 1;28(1):189-198. https://doi.org/10.1093/humrep/des381
Johannesson, L. ; Enskog, A. ; Mölne, J. ; Diaz-Garcia, C. ; Hanafy, A. ; Dahm-Kähler, P. ; Tekin, Akin ; Tryphonopoulos, P. ; Morales, P. ; Rivas, K. ; Ruiz, Phillip ; Tzakis, A. ; Olausson, M. ; Brännström, M. / Preclinical report on allogeneic uterus transplantation in non-human primates. In: Human Reproduction. 2013 ; Vol. 28, No. 1. pp. 189-198.
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