Transplant International最新文献

Induced pluripotent stem cell (iPSC)-derived pancreatic islets represent a promising therapeutic approach for restoring insulin independence in type 1 diabetes (T1D). However, their clinical success remains critically dependent on overcoming rejection mediated by innate and adaptive immune responses. Current immunosuppressive therapies pose significant long-term risks and only partially control alloimmune and autoimmune reactions. Targeted immunomodulation using monoclonal antibodies is a safer, more precise alternative. Here, we explored the impacts of blocking CD276 (B7-H3) and CD155 (PVR), activating ligands involved in immune recognition and regulation, on the survival and in vivo maturation of iPSC-derived endocrine progenitors (EPs) into functional pancreatic islets. Using a humanized mouse model, we demonstrated that dual blockade of CD276 and CD155 markedly reduced NK cell-mediated graft rejection, prevented CD14⁺ monocyte activation, and limited overall immune infiltration. In addition, CD155 blockade increased PD-1 levels on activated CD8⁺ T cells and significantly enhanced regulatory T cell (Treg) expansion and function, thereby promoting graft tolerance. Combined treatment prolonged engraftment and facilitated the maturation of EPs into functional, insulin-secreting cells, as indicated by increased human C-peptide levels and glucose responsiveness 4 weeks post-transplantation. Our findings highlight CD276/CD155 blockade as a novel immunomodulatory strategy to support tolerance and the functional maturation of iPSC-derived pancreatic grafts in T1D.

Since the first live birth in 2014 after uterus transplantation, the procedure has become a viable fertility treatment worldwide for the 1 in 500 women affected by absolute uterine factor infertility. In this review, we provide insight on Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) and the other conditions that lead to the development of AUFI. Additionally, we provide a comprehensive overview of the evolution of uterus transplantation from the first sporadic cases to the current clinical status of the procedure, and detail multiple aspects that go into a successful UTx. Furthermore, we review some of the more recent developments in this rapidly expanding field and evaluate the prospective direction of UTx.

Rescue of non-used kidneys may be facilitated using sub-normothermic acellular machine perfusion (SNAP), which can prolong safe preservation times and provide additional viability assessment. While blood-based normothermic machine perfusion (NMP) has been utilized internationally, barriers to adoption of NMP in the US include limited availability, staffing and facility resource limitations, geographic distances between donor and recipient hospitals, blood shortages, and reliance on hypothermic machine perfusion (HMP). To overcome obstacles to adoption, the first centralized kidney Assessment and Repair Center (ARC) was established in West Lafayette, Indiana. Organized as an independent public benefit company, this center was designed to provide sub-normothermic acellular perfusion (SNAP) and assessment services to rescue unused/hard-to-place (HTP) kidneys. An acellular, human serum albumin-based perfusate was chosen, and a second cold ischemic time (CIT) was validated during pre-clinical testing. Between April 2024- May 2025, 158 unused deceased donor kidneys were transported to the ARC, resulting in 142 transplants (90%) after SNAP assessment. SNAP is feasible when performed by a centralized ARC and reduces kidney discard rates by providing objective viability assessment data. Moreover, SNAP allows for extended preservation times of nearly 70 h, enabling improved logistical planning and broader sharing of deceased donor kidneys.

In four phase 2 clinical trials, patients underwent imlifidase-enabled kidney transplantation, converting a positive crossmatch (+XM) to negative. Here, we present data from 39 patients enrolled in the 5-year follow-up extension trial. Patient survival, graft survival, renal function, delayed graft function (DGF) antibody mediated rejection (AMR) frequency, safety and presence of donor specific antibodies (DSAs) are presented. Data from the long-term follow-up trial (17-HMedIdeS-14); NCT03611621) with planned visits at 1, 2, 3, and 5 years after imlifidase were combined with up to 6-month phase 2 data from 4 pivotal trials (13-HMedIdeS-02, 13-HMedIdeS-03, 14-HMedIdeS-04, 15-HMedIdeS-06). Five-year patient survival was 90% with 3 deaths occurring between 6 months and 1 year, with no deaths occurring subsequently. Death-censored graft survival was 82% (with 3 early graft losses and 3 graft losses between 2 and 5 years). Mean eGFR at 5 years was 50.1 (MDRD), 55.8 (CKD-EPI, 2021) and 52.5 (KRS, 2023) mL/min/1.73 m² (N = 24 patients) among functioning grafts. DSA rebounded with levels progressively decreasing over time and no increase in DSA seen between 3 and 5 years. No AMR occurred between 3 and 5 years. Furthermore, no additional safety signals assessed as related to imlifidase were reported in this cohort. At 5 years, highly-HLA sensitized patients who underwent imlifidase desensitization prior to transplantation demonstrated excellent patient and graft survival, despite their high-risk immunological profile. Imlifidase offers a viable and effective treatment option for highly sensitized patients to achieve life-saving transplantation and continued optimism is warranted.

Clinical trial: ClinicalTrials.gov (NCT02790437), EudraCT Number: 2016-002064-13.

Cytomegalovirus (CMV) serologic discordance is a known risk factor for adverse outcomes after solid-organ transplantation. This study evaluated outcomes of simultaneous pancreas-kidney (SPK) recipients based on donor and recipient CMV serostatus. Using the Scientific Registry of Transplant Recipients, we identified adult SPK recipients between 2014 and 2024 and categorized them as donor/recipient negative (D-/R-), recipient positive (R+), or donor positive/recipient negative (D+/R-). Patients with missing data, nonstandard immunosuppression, or positive crossmatch were excluded. Among 4,744 recipients (831 D-/R-, 2,671 R+, 1,242 D+/R-), the D+/R- group had the highest 1-year rates of graft rejection (16.6%, p = 0.02) and hospitalization (67.2%, p = 0.005), whereas the D-/R- group had the lowest (11.8% and 60.0%, respectively). In multivariable models, D+/R- recipients had higher risks of death (HR 1.28; 95% CI, 1 .01-1.62; p = 0.045), pancreas graft-loss (HR 1.25; 95% CI, 1.06-1.48; p = 0.009), and death-censored kidney graft-loss (HR 1.31; 95% CI, 1.01-1.69; p = 0.04) compared with R+. Conversely, D-/R- recipients had a lower risk of kidney graft-loss (HR 0.66; 95% CI, 0.46-0.96; p = 0.03). CMV D+/R- serostatus is independently associated with increased mortality and graft-loss after SPK transplantation. Matching CMV-seronegative donors with seronegative recipients may improve outcomes, warranting further study of the feasibility and broader impact of CMV serostatus-based-matching.

Cytomegalovirus (CMV) infection following solid organ transplant (SOT) is associated with increased mortality risk. In the phase 3 SOLSTICE study (NCT02931539), more transplant recipients achieved CMV clearance after 8 weeks with maribavir than investigator-assigned therapy (IAT). In SOLSTICE, SOT recipients with refractory CMV infection were randomized 2:1 to receive maribavir or IAT for 8 weeks. This post hoc analysis assessed the impact of CMV clearance at Week 8 on mortality at Week 20. Patients who achieved CMV clearance at Week 8 were categorized as responders, and patients without CMV clearance, or who received maribavir rescue or alternative treatment, were categorized as nonresponders. All-cause mortality was assessed at Week 20 for responders and nonresponders using the Kaplan-Meier method with log-rank test. The analysis included 211 SOT recipients: 97 responders and 114 nonresponders. Week 20 all-cause mortality was significantly higher in nonresponders than responders (p = 0.0024). No deaths were reported in the responder group, and 10 deaths were reported in the nonresponder group (3 receiving IAT, 7 receiving maribavir). Median (range) time from treatment start to death was 30.5 (3-123) days. This analysis is consistent with other studies showing an increased risk of mortality with post-SOT CMV infection.