Annette C. and Harold C. Simmons Transplant Institute

Jones, B. P., S. Saso, T. Bracewell-Milnes, M. Y. Thum, J. Nicopoullos, C. Diaz-Garcia, P. Friend, S. Ghaem-Maghami, G. Testa, L. Johannesson, I. Quiroga, J. Yazbek and J. R. Smith (2019). “Human Uterine Transplantation: A Review of Outcomes from the First 45 Cases.” BJOG 126(11): 1310-1319.

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Uterine transplantation restores reproductive anatomy in women with absolute uterine factor infertility and allows the opportunity to conceive, experience gestation, and acquire motherhood. The number of cases being performed is increasing exponentially, with detailed outcomes from 45 cases, including nine live births, now available. In light of the data presented herein, including detailed surgical, immunosuppressive and obstetric outcomes, the feasibility of uterine transplantation is now difficult to refute. However, it is associated with significant risk with more than one-quarter of grafts removed because of complications, and one in ten donors suffering complications requiring surgical repair. TWEETABLE ABSTRACT: Uterine transplantation is feasible in women with uterine factor infertility, but is associated with significant risk of complication.

Johannesson, L., A. Wall, J. M. Putman, L. Zhang, G. Testa and C. Diaz-Garcia (2019). “Rethinking the Time Interval to Embryo Transfer after Uterus Transplantation – Duets (Dallas Uterus Transplant Study).” BJOG 126(11): 1305-1309.

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Uterus transplant can allow women to carry their own pregnancy. Because of the transplant operation, infectious disease risks, and immunosuppressive medications, these pregnancies require careful planning. Conditions to achieve before ET include stable uterine graft function, absence of active rejection, stable immunosuppressive medication with agents with low teratogenic risk, and low‐risk status for harmful opportunistic infections. Our experience, the experience of other uterus transplant programmes, and results of successful pregnancies in other solid organ transplant recipients suggest ET could be considered as soon as 3 months after uterus transplantation if the above criteria are met. Given the unique characteristics of uterus transplantation and the recipient population, the transplant‐to‐ET interval should differ from recommendations in other organ and vascular allograft transplantations. The incentive of minimising the recipient‐graft time and concomitant exposure to immunosuppressants in this young, healthy patient population strongly supports shortening the transplant‐to‐ET time. (Excerpt from text, p. 1308; no abstract available.)

Hasan, M. M., L. Thompson-Snipes, G. Klintmalm, A. J. Demetris, J. O’Leary, S. Oh and H. Joo (2019). “Cd24(Hi)Cd38(Hi) and Cd24(Hi)Cd27(+) Human Regulatory B Cells Display Common and Distinct Functional Characteristics.” J Immunol 203(8): 2110-2120.

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Although IL-10-producing regulatory B cells (Bregs) play important roles in immune regulation, their surface phenotypes and functional characteristics have not been fully investigated. In this study, we report that the frequency of IL-10-producing Bregs in human peripheral blood, spleens, and tonsils is similar, but they display heterogenous surface phenotypes. Nonetheless, CD24(hi)CD38(hi) transitional B cells (TBs) and CD24(hi)CD27(+) B cells (human equivalent of murine B10 cells) are the major IL-10-producing B cells. They both suppress CD4(+) T cell proliferation as well as IFN-gamma/IL-17 expression. However, CD24(hi)CD27(+) B cells were more efficient than TBs at suppressing CD4(+) T cell proliferation and IFN-gamma/IL-17 expression, whereas they both coexpress IL-10 and TNF-alpha. TGF-beta1 and granzyme B expression were also enriched within CD24(hi)CD27(+) B cells, when compared with TBs. Additionally, CD24(hi)CD27(+) B cells expressed increased levels of surface integrins (CD11a, CD11b, alpha1, alpha4, and beta1) and CD39 (an ecto-ATPase), suggesting that the in vivo mechanisms of action of the two Breg subsets are not the same. Lastly, we also report that liver allograft recipients with plasma cell hepatitis had significant decreases of both Breg subsets.

Lawrence, M. C., C. M. Darden, S. Vasu, K. Kumano, J. Gu, X. Wang, J. Chan, Z. Xu, B. F. Lemoine, P. Nguyen, C. Smitherman, B. Naziruddin and G. Testa (2019). “Profiling Gene Programs in the Blood during Liver Regeneration in Living Liver Donors.” Liver Transpl Jul 24. [Epub ahead of print].

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The human liver’s capacity to rapidly regenerate to a full-sized functional organ after resection has allowed successful outcomes for living-donor liver transplantation (LDLT) procedures. However, the ability to detect and track physiological changes occurring during liver regeneration after resection and throughout the restoration process is still lacking. We performed a comprehensive whole-transcriptome RNA sequencing analysis of liver and circulating blood tissue from 12 healthy LDLT donors to define biomarker signatures for monitoring physiological activities during liver regeneration at 14 time points for up to 1 year procedural follow up. LDLT donor liver tissue differentially expressed 1238 coding and noncoding genes post resection, and an additional 1260 genes were selectively regulated post-LDLT. A total of 15,011 RNA transcript species were identified in the blood in response to liver resection. Transcripts most highly regulated were sequentially expressed within three distinct peaks that correlated with sets of functional genes involved in induction of liver resection-specific innate immune response (Peak I), activation of the complement system (Peak II), and platelet activation and erythropoiesis (Peak III). Each peak corresponded with progressive phases of extracellular matrix degradation, remodeling, and organization during liver restoration. These processes could be tracked by distinct molecular signatures of upregulated and downregulated gene profiles in the blood during phases of liver repair and regeneration. In conclusion, the results establish temporal and dynamic transcriptional patterns of gene expression following surgical liver resection that can be detected in the blood and potentially used as biomarker signatures for monitoring phases of liver regeneration.

Johannesson, L., A. Wall, J. M. Putman, L. Zhang, G. Testa and C. Diaz-Garcia (2019). “Rethinking the time interval to embryo transfer after uterus transplantation-DUETS (Dallas UtErus Transplant Study).” BJOG Jul 8. [Epub ahead of print].

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The first successful live birth after uterus transplantation occurred in 2014. Since then, successful live births have been replicated, offering hope to women with uterine factor infertility who want to carry a pregnancy . . . Uterus transplant can allow women to carry their own pregnancy. Because of the transplant operation, infectious disease risks, and immunosuppressive medications, these pregnancies require careful planning. Conditions to achieve before ET include stable uterine graft function, absence of active rejection, stable immunosuppressive medication with agents with low teratogenic risk, and low‐risk status for harmful opportunistic infections. Our experience, the experience of other uterus transplant programmes, and results of successful pregnancies in other solid organ transplant recipients suggest ET could be considered as soon as 3 months after uterus transplantation if the above criteria are met. Given the unique characteristics of uterus transplantation and the recipient population, the transplant‐to‐ET interval should differ from recommendations in other organ and vascular allograft transplantations. The incentive of minimising the recipient‐graft time and concomitant exposure to immunosuppressants in this young, healthy patient population strongly supports shortening the transplant‐to‐ET time. (Excerpts from text, p. 1, 4; no abstract available.)