With the increasing number of patients waiting for liver transplantation, donor shortage has become a serious problem. The use of grafts from marginal donors and donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. The benefits of hypothermic oxygenated machine perfusion (HOPE) in many clinical trials have been reported. On the other hand, normothermic machine perfusion (NMP) has been also performed and demonstrated to improve graft function. The application of preservation solution with artificial oxygen carrier solution under subnormothermic machine perfusion for marginal liver graft was shown. Furthermore, long-term maintaining of graft function or recovery by NMP enables ex vivo cell and gene therapy. Thus, machine perfusion technology may alleviate the not only preservation of marginal graft but also new ex vivo bioengineering.

Despite recent improvements in kidney transplantation outcomes, calcineurin inhibitor (CNI)-induced nephrotoxicity is one of the main issues to overcome to prevent renal allograft loss. Costimulatory blockade (CB) is expected to be an alternative agent to CNI. Among many types of CB agents, anti-CD154 antibody has a sufficient effect to suppress immunological response. However, it is not approved for clinical use due to thromboembolism caused by Fc receptor-mediated platelet activation. Although various types of anti-CD154 antibodies have been invented to overcome adverse events, no agents have had a sufficient immunosuppressive effect for allotransplantation. The newly developed anti-CD154 antibody, TNX-1500, was used in a kidney allotransplant model in cynomolgus macaques and was shown to inhibit rejection without a thromboembolism event. Furthermore, AT-1501 also demonstrated similar efficacy. The clinical application of these novel agents is expected to improve the outcome of renal transplantation.

Pulmonary fibrosis is a progressive disease caused by interstitial inflammation. In recent years, stem cell-based therapies have made dramatic progress as a curative treatment for pulmonary fibrosis. However, a highly sensitive imaging technique to investigate the in vivo dynamics of transplanted stem cells has not been established and remains unresolved. In this study, we administered adipose tissue-derived mesenchymal stem cells (ASCs) labeled with quantum dots (QDs: 8.0 nM), a nano quantum sensor, to a mouse model of bleomycin-induced pulmonary fibrosis in an attempt to clarify the relationship between the in vivo dynamics and therapeutic efficacy. The results showed that QDs-labeled ASCs stayed longer in bleomycin model mouse lungs and suppressed inflammation compared to normal lungs. In addition, 3D imaging revealed that transplanted stem cells accumulated in fibrotic regions of the lungs.

Studies reporting the clinical use and efficacy of machine perfusion for the repair and assessment of susceptible organs from the expanded criteria donors have increased dramatically. Although the usefulness of perfusion at various temperatures has been demonstrated, there are few studies comparing perfusion temperatures, making it difficult to select the optimal perfusion condition. Furthermore, there are not a few variations in protocols such as combination with simple cold storage, hypothermic perfusion with or without programmed rewarming, and normothermic perfusion. However, the target optimal pH values for these perfusion temperatures have not been established. This article outlines the changes in the pH of perfusion solution and intra- and extracellular fluids in relation to temperature, and present a path to determine the temperature-dependent optimal perfusion pH in organ perfusion.

In May 2023, NHK’s “Close-Up Today” program aired a report regarding the “Organ Mediation Case” and the unknown reality of travel transplantation, highlighting the shortage of organs. Despite the influence of COVID-19, there is an inherent reluctance to donate organs from donors after circulatory death (DCDs). Several reasons attributed to this reluctance include the following: declining number and aging of donor physicians, a necessity for rapid and reliable procedures (humans), criteria for selecting recipients with long waiting times (expectant), lack of incentives (financial), and responsibility for successful or unsuccessful transplantation (psychological). Unlike donation during brain death, DCD necessitates a certain degree of experience since the timing of the cardiac arrest and subsequent removal is not fixed; removal is sudden; and the circumstances vary for each case, including cannulation, intravascular perfusion, and autopsy, and requires flexible and rapid removal techniques. Owing to the efforts of JOT and others, the use of ECMO in cardiac arrest donation, machine perfusion preservation, and mutual aid systems for extractions has been steadily improving. The key to increasing the number of DCDs is to stop the prolonged mediation process and the declining birth rate and aging of transplant physicians. DCD will increase if the number of transplant physicians is increased through organ donation standardization via sharing human and time resources in organ transplantation, reforming and standardizing surgical materials and protocols, and changing the selection of recipients to allow for shorter placement timeframes.

The number of donation after cardiac death (DCD) has fallen dramatically in Japan. Meanwhile, some Western countries compensate for organ shortages by increasing the DCD. The main factors for this are the legislation allowing the withdrawal of life-sustaining therapy for end-stage patients and the induction of normothermic regional perfusion before retrieval. Unlike brain death, there are no strict rules for DCD in Japan, such as the timing of heparin administration, canulation, and handling of life support equipment for DCD. This European experience could provide a strategy for increasing the number of DCDs in Japan.