MSC-derived exosomes carrying sFgl2 alleviate acute rejection of mouse heart transplantation by regulating macrophage polarization.

A review of smart alginate-based biomaterials: Innovations and challenges in tissue engineering and regenerative medicine.

Heart allograft rejection: molecular diagnosis using intra-graft targeted gene expression profiling.

Diagnosis of Cardiac Transplant Rejection Using Point-of-Care Ultrasound.

Urine-derived stem cells: The biomedical research of endothelial and cardiovascular tissue.

Solid organ transplant patients require appropriate immunosuppression to sufficiently control the allorecognition of the graft. Two tests, the QuantiFERON Monitor (QFM) and the Torque teno virus load (TTVL) provide an option to monitor the strength of immunosuppression. TTVL and QFM were simultaneously determined in kidney transplant patients. Clinical data, microbiological and histopathological findings were collected from the patients' medical records. 128 TTVL and QFM values were quantified in 107 patients. 69 patients (54%) had recurrent infections in the previous 6 months, 19 (15%) had malignancies, 47 (37%) had a recent kidney biopsy and among them 17 (36%) had histologically proven graft rejection. Results showed that there was no significant correlation between TTVL and QFM (ρ = -0.169, p=0.061). In patients with histologically proven rejection, TTVL was significantly lower than in patients without rejection (3.64±2.45 vs. 5.02±1.67 log10 copies/mL, p=0.026), but there was no difference between the groups in QFM (1.63±0.67 vs. 1.55±0.80 log10 IU/mL, p=0.735). Patients with known malignancy had lower TTVL compared to patients without it (p=0.041). No statistically significant difference was observed in TTVL and patients with or without infections (p=0.278). QFM was not different in patients with or without infection or malignancy. TTVL as an immune marker was associated with transplant rejection. There were no clinically significant associations between QFM and rejection and TTVL or QFM with infections and malignancies. Further prospective studies should be performed to confirm these results.

BackgroundLifelong immunosuppressive therapy is required to prevent allograft rejection in organ transplantation. Current immunosuppressants effectively suppress adaptive and innate immune responses, but their broad, antigen-non-specific effects often result in severe off-target complications. It remains a significant unmet medical need in transplant medicine.ResultsIn this study we investigated immunosuppressant effects of four major immunosuppressant classes, including tacrolimus, prednisone, mycophenolate mofetil (MMF), and fingolimod (FTY), on the gut microbiome, metabolic pathways, lymphoid architecture and lymphocyte trafficking after up to 30-day chronic exposure. Despite their distinct mechanisms of action and not designed to target the gut, all immunosuppressive drugs induced profound and time-dependent alterations in both intestine gene expression and gut microbiome composition. Progressive alterations from moderate early, drug-specific changes to a strikingly convergent microbial dysbiosis, marked by significant expansion of pathobionts of Muribaculaceae, occurred across all drug classes. Concurrently, all drugs uniformly induced significant suppression of mucosal immunity including B cell, immunoglobulin, and antigen recognition. Time-dependent changes in lymph node (LN) reorganization and cellular composition were also observed, marked by a progressive shift toward pro-inflammatory phenotypes in gut-draining mesenteric LNs and a gradual loss of tolerogenic architecture in peripheral LNs. Drug-specific metabolic alterations and distinct phases of intestinal transcriptional responses were also characterized. Notably, MMF and FTY demonstrated the most robust immunomodulatory properties, and were able to acutely suppress alloantigen-induced inflammation through mediating regulatory T cell distribution and LN remodeling.ConclusionsTogether, our findings show that immunosuppressants elicit complex, time-dependent effects that remodel the gut and exert compartment-specific impacts on lymphoid tissues, differentially affecting gut-draining mesenteric versus peripheral LN. Understanding these relationships offers new opportunities for refining immunosuppressive strategies to reduce treatment-related off-target complications and improve long-term organ transplant outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12964-025-02517-0.

Allogeneic skin transplantation is a critical method for treating extensive burns, trauma, and skin defects; however, its success is severely limited by immune rejection, driven by complex interactions between innate and adaptive immunity. Macrophages, particularly their polarization states, play pivotal yet dual roles in this process. While M1 macrophages exacerbate inflammation and graft damage, M2-polarized macrophages emerge as critical regulators of immune tolerance. Manipulating macrophages to polarize into M2 can not only reduce graft rejection but also induce immune tolerance, thereby promoting graft survival. M2 macrophages effectively inhibit transplant rejection by secreting anti-inflammatory cytokines, suppressing T-cell activation, and fostering the differentiation of immunosuppressive cells. This review delineates the immunological basis of skin allograft rejection, the intrinsic mechanisms governing M2 polarization, and the role of M2 macrophages in inducing immune tolerance in allogeneic skin transplantation. The discussion provides a theoretical foundation for novel immunosuppressive strategies and underscores M2 macrophages as therapeutic targets to improve transplant outcomes, bridging mechanistic insights to clinical innovation. Safer and more effective immunomodulatory strategies are anticipated to increase the success rate of allogeneic skin transplantation and enhance patient quality of life.

Racial disparities in kidney transplant outcomes remain a persistent challenge despite advances in immunosuppression. This study examined short- and intermediate-term graft outcomes among Black and White recipients receiving cyclosporine plus mTOR inhibitor based regimens. Using the TriNetX Global Collaborative Network, we identified adult kidney transplant recipients, stratified cohorts by race (Black vs. White), matched 1:1 on demographics, comorbidities, and concomitant medications. Outcomes included transplant rejection, graft failure, and all-cause mortality at one year and between one to three years post-transplant. Analyses included risk differences, hazard ratios (HR), and Kaplan-Meier survival estimates. Matched cohorts included 305 Black and 305 White recipients. At one year, Black patients experienced significantly higher rejection (23.6% vs. 16.1%; HR 1.50, 95% CI 1.04-2.16) and graft failure (22.6% vs. 15.1%; HR 1.54, 95% CI 1.06-2.24), mortality was similar (6.9% vs. 8.9%, p = 0.367). Between one and three years, disparities persisted: rejection occurred in 21.3% of Black vs. 13.8% of White recipients (HR 1.69, 95% CI 1.15-2.49), and failure in 20.7% vs. 12.5% (HR 1.79, 95% CI 1.20-2.68). Mortality remained nonsignificant (10.2% vs. 8.2%, p = 0.400). Despite matched clinical profiles and immunosuppressive regimens, Black kidney transplant recipients experienced persistently higher rates of rejection and graft failure. These findings highlight persistent disparities in transplant outcomes and the need for equity-driven interventions to improve equity in graft survival.

The Banff classification for kidney transplant pathology dichotomizes the rejection continuum into distinct diagnostic categories, introducing artificial cutoff points and threshold effects. To better reflect the underlying disease spectrum, in this cohort study of 19,500 biopsies from 8873 patients across 10 centers worldwide, we developed two indices for quantifying antibody-mediated rejection/microvascular inflammation and T-cell-mediated rejection/tubulointerstitial inflammation from histological lesion scores and calculated indices for overall activity and chronicity. These indices demonstrate excellent discrimination for the main diagnostic categories of rejection (AUCs from 0.95 to 0.99), with consistent performance across derivation and validation datasets. These indices strictly confine intermediate phenotypes to low index values and are associated to graft failure even within the diagnostic categories, thus reflecting the underlying rejection continuum. In this work, we demonstrate that four continuous indices provide implementable and interpretable global evaluation of kidney transplant histology that align with the continuous nature of the rejection process regardless of the underlying disease cause.

The number of spousal donor transplantation (SDT) has increased since the early 1990s. Although the SDT is performed successfully today, several concerns remain regarding compatibility. In particular, in husband-to-wife donations, donor-specific antibodies (DSA) positivity may develop as a consequence of previous pregnancies, thereby posing a risk to graft survival. However, data on outcomes in recipients with a history of pregnancy and the development of DSA are limited. In this study, we aimed to compare the outcomes of transplantation between high-risk spouses and transplantation from living donors. This study was conducted in our Nephrology and Transplantation department. It involved 59 spousal donors and 72 living-related donors with donor-specific antibodies who were older than >18 years of age. We evaluated the consecutive patients who had kidney transplantation between 2010-2020. We analyzed data from 59 SDT with 72 living-related donor transplants (LRDT) with DSA positivity. Within the first year after transplantation, the acute rejection rate was highest in the husband-to-wife (H-to-W) group (p=0.01). Compared with LRDT, H-to-W transplants were associated with an increased risk of acute rejection [OR 95%CI:4.231(1.122-15.957)](p=0.03). Cox regression analysis demonstrated a higher risk of rejection in kidney transplants from H-to-W within the first year of kidney transplantation [HR:3.734(95%CI:1.087-12.825)(p=0.03)]. There was no increase in creatinine doubling time between groups and no increase in risk of rejection in 5 years. During the follow-up period, graft loss was reported in three patients, comprising two in the LRDT group and one in the W-to-H group. In conclusion, SDT, particularly when DSA has developed, appears to be associated with a higher risk of rejection during the first year compared with LRDT with similar DSA. Nevertheless, similar graft survival suggests that H-to-W spousal transplants appears to be safe in the long term.

Organ transplantation is a life-saving treatment for patients with end-stage organ failure but requires lifelong immunosuppression that can result in significant complications. Achieving stable and durable donor-specific tolerance, whereby immunosuppression can be stopped without precipitating graft rejection, holds the promise to circumvent these problems. While transient inhibition of the CD40/CD154 costimulatory pathway delays transplant rejection in animal models, and antibodies blocking this interaction are currently in clinical trials, the efficacy of anti-CD154 (αCD154) in mouse models is significantly enhanced by the addition of donor splenocyte transfusion (DST). Indeed, αCD154 + DST, but not αCD154 alone, can successfully induce donor-specific transplantation tolerance to fully mismatched cardiac allografts in mice. Why DST needs to be added to αCD154 is not fully understood. By integrating tracking of graft-specific T cells and of donor cells, we show that systemic, but not subcutaneous, injection of DST enables alloantigen dissemination to secondary lymphoid organs beyond those directly draining the transplant. This wider biodistribution results in a greater number of alloreactive T cells interacting with donor alloantigens in all lymphoid organs, such that more alloreactive T cells can be the target of CD154 blockade. Furthermore, the duration of DST persistence, facilitated by the sharing of MHC alleles between the donor and the recipient, emerges as a critical factor in promoting αCD154-mediated graft acceptance. These results provide insights into rational approaches to improve translation of αCD154 in the clinic.

The gene expression uncovering the molecular mechanism of liver transplantation (LT) rejection and immune tolerance remains unclear. The mice orthotopic LT rejection and tolerance models were established. Liver sections were obtained for transcriptome sequencing. A total of 2560 DEGs were identified in the rejection group. The major enrichment pathways included graft-versus-host disease, Th17 cell differentiation, T cell receptor signaling pathway and cytokine-cytokine receptor interaction. The screened top 10 hub genes, including Ctla4, Ifng, Gzmb, Pdcd1, cd28, cd8a, Tbx21, and Lag3, were associated with T cell cytotoxicity and exhaustion. The gene expression levels of functional characteristics of T cell exhaustion, including Il2ra, Tnf, and Ifng were all significantly decreased in the tolerance group. Flow cytometry confirmed the significantly higher expression of TIM-3 and PD-1 in CD8+ T cells. Immunohistochemical staining of liver tissues also showed remarkably increased granzyme-B-positive cells in the rejection group. A comprehensive molecular profiling of the immune alterations was observed, especially the dynamic change of CD8+ T cell-mediated cytotoxicity and exhaustion. This provides new insights into the molecular mechanism of LT rejection and immune tolerance.

Abstract Purpose of Review Extracorporeal photopheresis (ECP) is an immunomodulatory treatment in which an apheresis machine isolates mononuclear cells from whole blood that are then treated with psoralen and ultraviolet-A light and reinfused into the patient. ECP has been approved for use in cutaneous T-cell lymphoma (CTCL) for 30 years; it has also been shown to be effective for graft-versus-host disease, solid organ transplant rejection, and various autoimmune diseases. Nonetheless, ECP is relatively underutilized, perhaps due to knowledge gaps and resource limitations. Here, we review ECP indications and techniques, as well as the data supporting its use in clinical settings. Recent Finding Recent clinical studies have emphasized the durability of ECP in CTCL, both as monotherapy and in combination with topical and other systemic CTCL treatment modalities. New insights into the mechanism of action underlying ECP have illuminated its effects on both cellular and humoral immunity. Specific clinical and laboratory findings have been identified as potential predictors of ECP response. Summary ECP is a well-tolerated and effective treatment option for a growing list of indications. In CTCL, ECP can achieve durable responses with longer treatment courses and should be considered as a first-line option for erythrodermic disease and Sézary syndrome.

IntroductionIn tissue engineering, there is a growing need for patient-specific strategies that enable precise control of cellular behaviour — such as adhesion, proliferation, and migration — to enhance tissue integration and reduce transplant rejection. Engineering the physicochemical properties and topography of substrates is a promising way to guide cell responses. Among available materials, graphene nanoplatelets offer outstanding physicochemical, electrical, and mechanical properties, making them ideal for biomedical use. Moreover, printed electronics techniques allow efficient, cost-effective fabrication of continuous coatings or intricate micropatterns on flexible substrates.MethodsGraphene nanoplatelet patterns were fabricated on flexible thermoplastic polyurethane substrates using inkjet and aerosol jet printing to compare the methods and their influence on cell behaviour. Layers were analysed for morphology, topography, and electrical properties (SEM, Raman spectroscopy, profilometry, electrical measurements). Surface wettability and surface free energy were measured via contact angle measurements. L929 fibroblast cells were cultured on printed patterns and assessed by confocal microscopy and MTT assay.Results and DiscussionGraphene patterns significantly improved cell proliferation compared to TPU controls. Cells aligned and migrated along printed graphene features, especially on aerosol jet-printed patterns, which promoted attachment and spreading. Quantitative analysis confirmed enhanced cell coverage and proliferation, highlighting the potential of graphene micropatterns for precise cellular control in regenerative medicine.

Acute rejection (AR) of a kidney graft in renal transplant recipients is associated with microvascular injury leading to graft dysfunction and failure. Long noncoding RNAs (lncRNAs) may serve as markers for vascular injury and AR. We aimed to identify lncRNA biomarkers associated with graft loss after renal transplantation. We searched PubMed, Scopus, Embase, and Web of Science. Odds ratios (ORs), hazard ratios (HRs), and their 95% confidence intervals (95% CIs) were calculated to assess effect sizes. All graphical designs and statistical analyses were performed using STATA version 17 (StataCorp LP, College Station, TX, USA) and the meta package. Of 291 initially identified articles, 10 met eligibility criteria and were included in the systematic review; 3 provided sufficient data for meta‑analysis. The pooled area under the curve (AUC) for lncRNA measurement in diagnosing acute kidney rejection was 0.79 in adults and 0.75 in pediatric populations, indicating good diagnostic accuracy. Leave‑one‑out sensitivity analyses confirmed the stability of these findings. However, the pooled HR for the prognostic value of lncRNAs was 0.81 (95% CI: 0.63-1.04), which was not statistically significant. Assessment of lncRNA levels in plasma or urine appears promising as a diagnostic biomarker for acute kidney rejection. The prognostic value of lncRNAs in the course of acute kidney rejection requires further evaluation.

NLRX1 as a novel therapeutic target: TRAF6-dependent inhibition of acute rejection in rat liver transplantation.

Background: In kidney transplant recipients sensitized to donor antigens, graft rejection remains a leading cause of allograft failure. The presence of preformed antibodies against donor human leukocyte antigen (HLA) molecules predisposes these patients to heightened immune-mediated rejection of the allograft. Careful consideration of individual risk factors, along with the judicious use ofimmunosuppressive therapies, is essential to improving transplant outcomes in sensitized patients. Objectives: To identify the factors contributing to graft rejection in HLA-sensitized kidney transplant recipients and to evaluate the most effective immunosuppressive strategies for this high-risk population. Methodology:This cross-sectional study was conducted at the January 2023 to January 2024.out of 100 patients Data were collected from HLA-sensitized kidney transplant recipients to assess risk factors for graft rejection and evaluate the effectiveness of different immunosuppressive strategies. Results: Total 100 patients mean age of participants was 47.8 ± 12.4 years and S/D of 12.4 years). The rate of rejection was much higher for sensitized participants (p < 0.01) compared to individuals who were not sensitized. Whereas elevated DSA and a history of previous transplants were helpful in predicting rejection. The outcomes showed that using plasmapheresis, IVIg and induction therapy helped improve the survival of grafts (p = 0.03). Conclusion: HLA sensitization markedly increases the risk of graft rejection in kidney transplant recipients. When rejection is spotted early and the right immunosuppressant therapies are used, the chances of rejection and graft loss are lowered.

Background: Cardiac allograft vasculopathy (CAV) and transplant rejection are major contributors to late morbidity and mortality following heart transplantation. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) offer cardiovascular benefits in various populations, but their safety and impact on heart transplant recipients remain poorly defined. Methods: Using the TriNetX Global Collaborative Network, which utilizes healthcare data from 144 healthcare institutions, we conducted a retrospective cohort study of adult heart transplant recipients. Exposure was defined as initiation of SGLT2i therapy within 5 years after transplant (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin). Propensity score matching (1:1) was performed on 31 covariates including demographics, immunosuppressive agents, comorbidities, and baseline labs. Outcomes were analyzed using Kaplan-Meier and Cox proportional hazard models over a 3-year follow-up window. The primary outcome was CAV (T86.290); secondary outcomes included all-cause mortality, transplant rejection, and hospitalization. Results: After matching, 315 patients per group were included. Median follow-up was longer in the SGLT2 group (960 vs 733 days). CAV rates were similar in both groups (16.8% of SGLT2 users vs 12.1% of controls, HR 1.17, 95% CI: 0.76–1.80; p = 0.47). SGLT2i use was associated with significantly lower all-cause mortality (10.8% vs. 17.5%; HR 0.53, 95% CI: 0.34–0.81; p = 0.023), reduced hospitalizations (HR 0.58, 95% CI: 0.48–0.69; p < 0.001), and decreased rejection rates (HR 0.71, 95% CI: 0.56–0.90; p = 0.002). Conclusion: In this multicenter real-world cohort of heart transplant recipients, SGLT2 inhibitor use was associated with significantly reduced all-cause mortality, rejection and hospitalization, without an increase in transplant rejection. There was no significant increase in CAV. These findings support the potential role of SGLT2i as a safe adjunct in selected post-transplant patients.

Background: Racial and gender disparities in heart transplant access and outcomes were well documented prior to 2018. On October 18, 2018, the United Network for Organ Sharing (UNOS) implemented a revised Adult Heart Allocation Policy aimed at improving equity. This study examines whether such disparities have persisted in the post-policy era. Method: A retrospective cohort study was conducted using data from the United States TriNetX platform, which aggregates records from 66 healthcare organizations. Heart transplant recipients from 2018 to 2023 were identified and stratified by gender and race. Propensity score matching was used to balance baseline characteristics between groups. The primary outcome was all-cause mortality, while secondary outcomes included heart failure and all-cause hospitalization, transplant rejection, sepsis and end-stage renal disease. Hazard ratios were calculated using Cox proportional hazards models. Results: Between 2018 and 2023, a total of 2,569 heart transplant recipients were identified, including 1,862 males (72.5%) and 707 females (27.5%). The racial distribution included 1,414 White (55.0%), 722 African American (28.1%), 216 Hispanic (8.4%), and 56 Asian (2.2%) patients. No significant differences in mortality were observed across sex or racial groups. However, female recipients had significantly higher risks of adverse outcomes compared to males, including heart failure (HR = 1.59, 95% CI: 1.11–2.28), transplant rejection (HR = 1.26, 95% CI: 1.09–1.46), and rehospitalization (HR = 1.21, 95% CI: 1.07–1.38). African American recipients experienced a significantly lower rate of transplant rejection compared to White recipients (HR = 0.72, 95% CI: 0.62–0.84, p < 0.001). There were no statistically significant differences in heart failure hospitalization, ESRD, or all-cause hospitalization among racial groups. Conclusions: The findings suggest that while disparities in heart transplant outcomes have improved since the 2018 allocation policy change, significant gaps remain. Female recipients continue to face higher risks of adverse outcomes, and although racial differences in mortality were not observed, certain disparities—such as in transplant rejection rates—persist. These results highlight progress toward equity but underscore the need for continued efforts to eliminate sex- and race-based differences in post-transplant outcomes fully.