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Molecular Mechanisms in Organ Transplantation
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Molecular Mechanisms in Organ Transplantation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 25 November 2025 | Viewed by 2445

Special Issue Editor

Dr. Hirofumi Hirao

E-Mail Website
Guest Editor
Department of Surgery, Division of Hepato-Pancreato-Biliary Surgery and Transplantation, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Interests: liver transplantation; immune response; rejection; ischemia-reperfusion injury

Special Issue Information

Dear Colleagues,

Transplantation has become one of the standard treatments for irreversible organ failure. However, during the perioperative period, grafts are exposed to multifaceted stresses, e.g., cold stress during static preservation, warm ischemia-reperfusion injury, activation of innate/adaptive immunity, and circulatory disturbance associated with disorders in the coagulation system. Susceptibility to graft damage depends on the type of cells and organs.

For example, the acceptable cold ischemic time varies depending on the transplanted organ: 4 hours for the heart, 8 hours for the lungs, 12 hours for the liver and small intestine, and 24 hours for the pancreas and kidneys. Fat deposition, especially in the liver, is a significant problem. The small intestine has a complex immune defense system, making it challenging to control rejection compared to other organ transplants. Hence, it is essential to understand cell-specific molecular mechanisms in response to perioperative stresses. This Special Issue aims to shed light on an emerging field with translational potential for a broad range of disciplines beyond transplantation.

Dr. Hirofumi Hirao
Guest Editor

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Keywords

  • organ transplantation
  • cellular-specific response to perioperative stress
  • cold/warm ischemia
  • innate/adaptive immunity
  • microcirculatory disturbance

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Published Papers (3 papers)

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Research

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16 pages, 2646 KiB  
Article
Comparison of Regulatory T-Cell Subpopulations in Antithymocytic Globulin Versus Post-Transplant Cyclophosphamide for Preventing Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation—A Retrospective Study
by Bu-Yeon Heo, Jeong Suk Koh, Su-Young Choi, Thi Thuy Duong Pham, Sang-Woo Lee, Jung-Hyun Park, Yunseon Jang, Myung-Won Lee, Seul-Bi Lee, Wonhyoung Seo, Deog-Yeon Jo, Jaeyul Kwon and Ik-Chan Song
Int. J. Mol. Sci. 2025, 26(6), 2521; https://doi.org/10.3390/ijms26062521 - 11 Mar 2025
Viewed by 589
Abstract
Antithymocytic globulin (ATG) and post-transplant cyclophosphamide (PTCy) are frequently used regimens for graft-versus-host disease (GVHD) prophylaxis. However, there is a lack of data about the difference in regulatory T-cell (Treg) subpopulations between these two regimens. Peripheral blood samples were collected on day +21 [...] Read more.
Antithymocytic globulin (ATG) and post-transplant cyclophosphamide (PTCy) are frequently used regimens for graft-versus-host disease (GVHD) prophylaxis. However, there is a lack of data about the difference in regulatory T-cell (Treg) subpopulations between these two regimens. Peripheral blood samples were collected on day +21 following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and the Treg subpopulations were analyzed using flow cytometry. The Treg populations were categorized into three distinct subgroups: naïve, effector, and non-suppressive. And we compared overall survival (OS), the cumulative incidence of acute and chronic GVHD, and the relapse rate between the ATG and PTCy groups. We enrolled 45 patients (28 in ATG, 17 in PTCy) in total. In the ATG group, 16 and 12 patients underwent human leukocyte antigen (HLA) matched-sibling donor and unrelated donor HSCT, respectively. In the PTCy group, 12 patients underwent haplo-identical HSCT, and 5 patients underwent HLA-matched unrelated donor HSCT. The cumulative incidence of Grade 2–4 acute GVHD was 18.3% in the ATG group compared to 38.1% in the PTCy group (p = 0.13), while severe chronic GVHD occurred in 19.4% of ATG patients and 41.7% of PTCy patients (p = 0.343). And OS and the relapse rate were not statistically different between the two groups. The conventional CD25+FOXP3+Treg count of CD4 + T cells was higher in the PTCy group than in the ATG group (p = 0.0020). The effector Treg subset was significantly higher in the PTCy group than in the ATG group (p = 0.0412). And the effector Treg cell count had an inverse correlation with the severity of acute GVHD (p = 0.0007). Effector Tregs may be used as a biomarker to predict the severity of acute GVHD after allo-HSCT. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Organ Transplantation)
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11 pages, 1540 KiB  
Article
Circulating Immune Complexes and Complement Activation in Sensitized Kidney Transplant Recipients
by Maria Stella Trivyza, Charikleia Stergiopoulou, Sotiris Tsakas, Theodoros Ntrinias, Marios Papasotiriou, Nikolaos Karydis, Evangelos Papachristou and Dimitrios S. Goumenos
Int. J. Mol. Sci. 2024, 25(20), 10904; https://doi.org/10.3390/ijms252010904 - 10 Oct 2024
Viewed by 1045
Abstract
Chronic antibody-mediated rejection in kidney transplantation is a common cause of graft loss in the late post-transplant period. In this process, the role of the classical complement activation pathway is crucial due to the formation of immune complexes between donor-specific antibodies (DSAs) and [...] Read more.
Chronic antibody-mediated rejection in kidney transplantation is a common cause of graft loss in the late post-transplant period. In this process, the role of the classical complement activation pathway is crucial due to the formation of immune complexes between donor-specific antibodies (DSAs) and donor antigens and the attachment of the C1q complement fragment. This study aimed to determine the levels of circulating C1q immunocomplexes (CIC-C1q) and complement activation (CH50), in sensitized kidney transplant recipients (KTRs). In this cross-sectional study we used serum samples from KTRs with de novo or preformed DSAs (n = 14), KTRs without DSAs (n = 28), and 22 subjects with no history of chronic kidney disease (controls). C1q immunocomplexes and CH50 concentration in serum were measured with the enzyme immunoassay (EIA) kit MicroVue CIC-C1q (Quidel, Athens, OH, USA) and EIA kit MicroVue CH50 (Quidel, OH, USA), respectively. Higher concentrations of CIC-C1q was observed in KTRs with DSAs in comparison with controls and with KTRs with no DSAs (6.8 ± 2.7 and 4.8 ± 1.9 vs. 5.0 ± 1.2 μg Eq/mL, respectively, p < 0.01). We found no difference in CIC-C1q between KTRs with no DSAs and controls. CIC-C1q levels were positively correlated with DSA titer. CH50 levels were decreased in KTRs with DSAs in comparison with controls and KTRs with no DSAs (39 ± 15 vs. 68 ± 40 and 71 ± 34 U Eq/mL, respectively, p < 0.01). There was no difference in CH50 between DSA-negative KTRs and controls. Kidney transplant recipients with DSAs had increased serum levels of C1q immunocomplexes and increased classical pathway complement activation. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Organ Transplantation)
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Review

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19 pages, 885 KiB  
Review
Tolerogenic Therapies in Cardiac Transplantation
by Laurenz Wolner, Johan William-Olsson, Bruno K. Podesser, Andreas Zuckermann and Nina Pilat
Int. J. Mol. Sci. 2025, 26(9), 3968; https://doi.org/10.3390/ijms26093968 - 23 Apr 2025
Viewed by 288
Abstract
Heart transplantation remains the gold-standard treatment for end-stage heart failure, yet long-term graft survival is hindered by chronic rejection and the morbidity and mortality caused by lifelong immunosuppression. While advances in medical and device-based therapies have reduced the overall need for transplantation, patients [...] Read more.
Heart transplantation remains the gold-standard treatment for end-stage heart failure, yet long-term graft survival is hindered by chronic rejection and the morbidity and mortality caused by lifelong immunosuppression. While advances in medical and device-based therapies have reduced the overall need for transplantation, patients who ultimately require a transplant often present with more advanced disease and comorbidities. Recent advances in tolerance-inducing strategies offer promising avenues to improve allograft acceptance, while minimizing immunosuppressive toxicity. This review explores novel approaches aiming to achieve long-term immunological tolerance, including co-stimulation blockade, mixed chimerism, regulatory T-cell (Treg) therapies, thymic transplantation, and double-organ transplantation. These strategies seek to promote donor-specific unresponsiveness and mitigate chronic rejection. Additionally, expanding the donor pool remains a critical challenge in addressing organ shortages. Innovations such as ABO-incompatible heart transplantation are revolutionizing the field by increasing donor availability and accessibility. In this article, we discuss the mechanistic basis, clinical advancements, and challenges of these approaches, highlighting their potential to transform the future of heart transplantation with emphasis on clinical translation. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Organ Transplantation)
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