Field Of Organ Transplantation Research Articles

Paul I. Terasaki, Ph.D: a pioneer in transplant medicine and a dedicated philanthropist

In the last five decades, remarkable surgical and medical advances ensued within the field of organ transplantation. These strides were marked by significant breakthroughs in transplant immunology, with Dr. Paul I. Terasaki standing as a true pillar of the field. This article highlights major milestones in Dr. Terasaki's life, his groundbreaking accomplishments in the field of transplant medicine, and his enduring philanthropic contributions to numerous medical and community organizations.

The Inhibition of Interfacial Ice Formation and Stress Accumulation with Zwitterionic Betaine and Trehalose for High-Efficiency Skin Cryopreservation.

Cryopreservation is a promising technique for the long-term storage of skin. However, the formation of ice crystals during cryopreservation unavoidably damages skin structure and functionality. Currently, the lack of thorough and systematic investigation into the internal mechanisms of skin cryoinjury obstructs the advancement of cryopreservation technology. In this study, we identified 3 primary contributors to skin cryoinjury: interfacial ice nucleation, stress accumulation, and thermal stress escalation. We emphasized the paramount role of interfacial ice nucleation in provoking ice growth within the skin during the cooling process. This progress subsequently leads to stress accumulation within the skin. During the rewarming process, the brittleness of skin, previously subjected to freezing, experienced a marked increase in thermal stress due to ice recrystallization. Based on these insights, we developed a novel zwitterionic betaine-based solution formulation designed for cryopreservation skin. This cryoprotective agent formulation exhibited superior capability in lowering ice nucleation temperatures and inhibiting ice formation at interfaces, while also facilitating the growth of smooth and rounded ice crystals compared to sharp-edged and cornered crystals formed in aqueous solutions. As a result, we successfully achieved prolonged cryopreservation of the skin for at least 6 months, while preserving 98.7% of structural integrity and 94.7% of Young's modulus. This work provides valuable insights into the mechanisms of ice crystal damage during organ cryopreservation and profoundly impacts the field of organ transplantation and regenerative medicine.

ESOT Roadmap for Advanced Therapy Medicinal Products in Transplantation: Navigating Regulatory Challenges to Enhance Access and Care.

The field of organ transplantation is experiencing a transformative shift with the rise of Advanced Therapy Medicinal Products (ATMPs), which include gene therapies, somatic cell therapies, and tissue-engineered products. These therapies offer new, potentially curative treatments for longstanding medical challenges, impacting numerous patients. However, their adoption is hindered by complex regulatory frameworks, high production costs, and inconsistent access across Europe. The ESOT ATMP Task Force's position paper analyzes these challenges from research to clinical application, advocating for a coordinated strategy to position Europe as a leader in ATMP development. It proposes specific actions such as streamlining regulatory pathways to accelerate approvals, boosting funding for ATMP research, and creating specialized facilities for development and implementation. The paper also highlights the critical roles of patient engagement and real-world evidence in optimizing clinical and regulatory practices.

Beyond the Pump: A Narrative Study Exploring Heart Memory.

The field of organ transplantation, particularly heart transplantation, has brought to light interesting phenomena challenging traditional understandings of memory, identity, and consciousness. Studies indicate that heart transplant recipients may exhibit preferences, emotions, and memories resembling those of the donors, suggesting a form of memory storage within the transplanted organ. Mechanisms proposed for this memory transfer include cellular memory, epigenetic modifications, and energetic interactions. Moreover, the heart's intricate neural network, often referred to as the "heart brain," communicates bidirectionally with the brain and other organs, supporting the concept of heart-brain connection and its role in memory and personality. Additionally, observations from hemispherectomy procedures highlight the brain's remarkable plasticity and functional preservation beyond expectations, further underscoring the complex interplay between the brain, body, and identity. However, ethical and philosophical questions regarding the implications of these findings, including the definition of death and the nature of personal identity, remain unresolved. Further interdisciplinary research is needed to unravel the intricacies of memory transfer, neuroplasticity, and organ integration, offering insights into both organ transplantation and broader aspects of neuroscience and human identity. Understanding these complexities holds promise for enhancing patient care in organ transplantation and deepens our understanding of fundamental aspects of human experience and existence.

Mesenchymal Stem Cells and Extracellular Vesicles: Therapeutic Potential in Organ Transplantation.

At present, organ transplantation remains the most appropriate therapy for patients with end-stage organ failure. However, the field of organ transplantation is still facing many challenges, including the shortage of organ donors, graft function damage caused by organ metastasis, and antibody-mediated immune rejection. It is therefore urgently necessary to find new and effective treatment. Stem cell therapy has been regarded as a "regenerative medicine technology." Mesenchymal stem cells (MSCs), as the most common source of cells for stem cell therapy, play an important role in regulating innate and adaptive immune responses and have been widely used in clinical trials for the treatment of autoimmune and inflammatory diseases. Increasing evidence has shown that MSCs mainly rely on paracrine pathways to exert immunomodulatory functions. In addition, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are the main components of paracrine substances of MSCs. Herein, an overview of the application of the function of MSCs and MSC-EVs in organ transplantation will focus on the progress reported in recent experimental and clinical findings and explore their uses for graft preconditioning and recipient immune tolerance regulation. Additionally, the limitations on the use of MSC and MSC-EVs are also discussed, covering the isolation of exosomes and preservation techniques. Finally, the opportunities and challenges for translating MSCs and MSC-EVs into clinical practice of organ transplantation are also evaluated.

Donation after Brain Death and Circulatory Death in Turkey: Current Status.

Tissue and organ transplantation is the best treatment option for end-stage organ failure. However, organ shortage still remains to be the greatest challenge facing the field of organ transplantation. Millions of people die and are buried with healthy organs, which could save the lives of many patients who continue to wait on transplant lists. Countries must aim to work towards a system of matching organs as much as possible with the deceased donation to meet the growing demand for organs. This action will not only result in the reduction of organ trafficking activities but shall also make an enormous difference to those patients awaiting transplants where living organ donors are not an option. Donation after circulator death (DCD) has gained much attention over the last decade as one of the accepted practices in order to expand the donor pool. DCD donation takes place after declaration of death using cardio-respiratory criteria in contrast to donation after brain death (DBD) where neurological criteria are used. Although DCD remains a focus of interest and contributes to donor numbers in many countries, it also poses many challenges medically, ethically and legally.

Race, ethnicity, ancestry, and aspects that impact HLA data and matching for transplant.

Race, ethnicity, and ancestry are terms that are often misinterpreted and/or used interchangeably. There is lack of consensus in the scientific literature on the definition of these terms and insufficient guidelines on the proper classification, collection, and application of this data in the scientific community. However, defining groups for human populations is crucial for multiple healthcare applications and clinical research. Some examples impacted by population classification include HLA matching for stem-cell or solid organ transplant, identifying disease associations and/or adverse drug reactions, defining social determinants of health, understanding diverse representation in research studies, and identifying potential biases. This article describes aspects of race, ethnicity and ancestry information that impact the stem-cell or solid organ transplantation field with particular focus on HLA data collected from donors and recipients by donor registries or transplant centers.

Machine perfusion preservation highlights from the Congress of the European Society of Organ Transplantation 2023.

The 21st Congress of the European Society of Organ Transplantation (ESOT), held on September 17-20th, 2023, in Athens, Greece, was a pivotal event in transplantation, focusing on the theme "Disruptive Innovation, Trusted Care." The congress attracted a global audience of 2 826 participants from 82 countries, emphasizing its international significance. Machine perfusion, as a groundbreaking technology in organ transplantation, was one of the central focuses of the conference. This year's meeting had a remarkable increase in accepted abstracts on machine perfusion, evidencing its growing prominence in the field. The collective findings from these abstracts highlighted the efficacy of machine perfusion in improving organ viability and transplant outcomes. Studies demonstrated improvements in graft survival and reduction in complications, as well as novel uses and techniques. Furthermore, the integration of machine perfusion with regenerative medicine and its application across multiple organ types were significant discussion points. The congress also highlighted the challenges and solutions in implementing machine perfusion in clinical settings, emphasizing the importance of practical training and international collaboration for advancing this technology. ESOT 2023 served as a crucial platform for disseminating scientific advancements, fostering practical learning, and facilitating international collaborations in organ transplantation. The congress underscored the evolution and importance of machine perfusion technology, marking a significant step forward in enhancing patient outcomes in the field of organ transplantation.

Applications, advancements, and challenges of 3D bioprinting in organ transplantation.

To date, organ transplantation remains an effective method for treating end-stage diseases of various organs. In recent years, despite the continuous development of organ transplantation technology, a variety of problems restricting its progress have emerged one after another, and the shortage of donors is at the top of the list. Bioprinting is a very useful tool that has huge application potential in many fields of life science and biotechnology, among which its use in medicine occupies a large area. With the development of bioprinting, advances in medicine have focused on printing cells and tissues for tissue regeneration and reconstruction of viable human organs, such as the heart, kidneys, and bones. In recent years, with the development of organ transplantation, three-dimensional (3D) bioprinting has played an increasingly important role in this field, giving rise to many unsolved problems, including a shortage of organ donors. This review respectively introduces the development of 3D bioprinting as well as its working principles and main applications in the medical field, especially in the applications, and advancements and challenges of 3D bioprinting in organ transplantation. With the continuous update and progress of printing technology and its deeper integration with the medical field, many obstacles will have new solutions, including tissue repair and regeneration, organ reconstruction, etc., especially in the field of organ transplantation. 3D printing technology will provide a better solution to the problem of donor shortage.

Unveiling transplantation research productivity of United States: A bibliometric analysis.

The United States has witnessed significant advancements in the field of organ transplantation over the course of the last five decades, as demonstrated by a notable increase in the quantity of academic research. The presence of a highly dynamic research environment necessitates continuous evaluations to maintain the integrity and progress of the field. To evaluate the total output and thematic emphasis of transplant research conducted in the United States. On January 10, 2023, we conducted a bibliometric search of United States research output in transplantation journals from the Web of Science database's Science Citation Index Expanded. We excluded editorials, meeting abstracts, and other non-article types. We analyzed annual trends, authors, institutions, articles, keywords, and countries collaborating with the United States, using VOSviewer 1.6.18 to create figures and tables. The United States published 25956 papers (3078 reviews and 22878 articles) representing 37.7% of the world's scientific output. Canada emerged as the top collaborator with the United States, co-authoring 1263 articles. Leading institutions in United States transplantation research were the University of Pittsburgh (1749 articles), Mayo Clinic (1605 articles), Harvard Medical School (1549 articles), and Johns Hopkins University (1280 articles). The top three keywords with over 2000 occurrences were "recipients," "survival," and "outcomes," indicating a focus on graft and recipient outcome markers by United States researchers. Our findings demonstrate the United States leadership in organ transplantation research, contributing significantly to the global scientific output in this field. However, opportunities exist for fostering expansive partnerships, particularly with developing countries. This study provides valuable insights into the transplantation research landscape in the United States, emphasizing the importance of ongoing evaluations to maintain and propel advancements in this critical medical discipline. The results may facilitate future collaborations, knowledge exchange, and the pursuit of innovative solutions in the realm of organ transplantation.

Should we abandon therapeutic drug monitoring of tacrolimus in whole blood and move to intracellular concentration measurements?

The measurement of whole blood (WB) concentrations has been the primary method for therapeutic drug monitoring of tacrolimus since its introduction in the field of organ transplantation. However, >99% of tacrolimus measured in WB is bound to erythrocytes and plasma proteins, which are the pharmacologically inactive fractions. The pharmacologically active fractions, the free (or unbound) tacrolimus in plasma and the intracellular tacrolimus, make up 1% or less of the WB concentration. The mechanism of action of tacrolimus is to inhibit the enzyme calcineurin within T lymphocytes and, therefore, measuring the intralymphocytic tacrolimus concentration may better reflect its pharmacodynamic effects and better correlate with clinical outcomes. However, studies on intracellular tacrolimus concentrations have shown conflicting results. In this review, we argue that we need to overcome the analytical limitations of current assays for the measurement of intracellular tacrolimus before moving this technique into the clinical setting. The validity and standardization of the cell isolation process before the measurement of the intracellular tacrolimus concentration is as important as the measurement itself but has received little attention in our view. Recent evidence suggests that the addition of an inhibitor of P-glycoprotein, an efflux transporter expressed on lymphocytes, prevents the expulsion of tacrolimus during the cell isolation process. Refining the technique for the intracellular tacrolimus concentration measurement should be the focus followed by clinical evaluation of its association with rejection risk.

Successful Orthotopic Liver Transplantation in Mice Utilizing Microcomputed Tomography Angiography.

Microcomputed tomography (microCT) angiography is an invaluable resource to researchers. New advances in this technology have allowed for high-quality images to be obtained of micro-vasculature and are high-fidelity tools in the field of organ transplantation. In this model of orthotopic liver transplantation (OLT) in mice, microCT affords the opportunity to evaluate allograft anastomosis in real time and has the added benefit of not having to sacrifice study animals. The choice of contrast, as well as image acquisition settings, create a high-definition image, which gives researchers invaluable information. This allows for evaluation of the technical aspects of the procedure as well as potentially evaluating different therapeutics over an extended duration of time. In this protocol, we detail an OLT model in mice in a stepwise fashion and finally describe a microCT protocol that can give high-quality images, which aid researchers in in-depth analysis of solid organ transplantation. We provide a step-by-step guide for liver transplantation in a mouse, as well as briefly discuss a protocol for evaluating the patency of the graft through microCT angiography.

Phenomenon of Demikhov. At N.V. Sklifosovsky Institute (1960–1986). V.P. Demikhov and his experiments in the field of organ transplantation in 1968–1973

The article analyzes the experimental studies of V.P. Demikhov conducted by him in 1968-1973, by studying the content of his report on the work done during this period of time and presented at the Meeting of the Academic Council of N.V. Sklifosovsky Institute in July 1973 for the re-election for the position of the Head of the Organ Transplantation Laboratory for a new 5-year term. It follows from the analyzed document that the extent of the research made by V.P. Demikhov and his staff significantly exceeded the data that were presented in the Institute's reporting documents for 1973, in the Research Plans for 1974, and the plans for implementing the research results in healthcare practice in 1974. The Table that illustrated the report indicated that in 1968–1973 V.P. Demikhov conducted more than 485 different experiments, including transplantation of vital organs, experiments on perfusion of isolated organs, resuscitation of cadaveric hearts, and heterogeneous blood transfusion. He actively collaborated with surgeons from many clinical institutions in Moscow (Institute of Tuberculosis, S.P. Botkin Hospital, Hospitals of the Moscow Military District) and other cities of the country (Frunze, Tyumen), conducting joint experimental and clinical studies with them. However, attempts to introduce the methods developed by him into clinical practice were futile. Of all his achievements in different years, the method of upper limb reimplantation was successfully applied in clinic in 1971 by Professor B.D. Komarov.

Phenomenon of Demikhov. At N.V. Sklifosovsky Institute (1960–1986). V.P. Demikhov and his experiments in the field of organ transplantation in 1971–1972

Having reviewed the archival documents, we enlightened the results of research performed by V.P. Demikhov and the employees of the Organ Transplantation Laboratory at the N.V. Sklifosovsky Research Institute, as well as V.P. Demikhov’s life and work in 1971–1972. During those years he continued to conduct the research required, as he believed, for practical healthcare. In 1971, together with M.M. Razgulov, he proposed a method for connecting blood vessels, a method for transplanting an upper limb together with a scapula, repeated experiments previously carried out on dogs, on human corpses (revitalization of a cadaveric heart, monitoring its activity using electrocardiography, implanting an additional heart into the cadaver’s chest in order to implement the technique in clinic for the treatment of heart failure), presented the results of his research at the X International Congress on Cardiovascular Diseases. We have also shown that in 1971–1972 V.P. Demikhov performed 76 experimental interventions, most of which were aimed at the development of a technique for transplanting an isolated cardiopulmonary complex and heart, as well as the technique for their revitalization. It should be noted that all the methods of organ transplantation developed by him were intended for implementation in clinic. However, no method was introduced into clinic during his lifetime. The fact is that the studies of V.P. Demikhov in the field of organ transplantation could not be adequately supplied from the material, technical and economic point, since they did not correspond to the main trends of the scientific and practical activities of the N.V. Sklifosovsky Institute – to improve the organizing system of rendering an emergency and urgent care to the population of Moscow in acute diseases and injuries.

Editorial introductions.

Current Opinion in Organ Transplantation was launched in 1996. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of organ transplantation is divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Editors-in-Chief, Associate Editor and Section Editors for this issue. SECTION EDITORS Matthew HartwigMatthew HartwigDr. Hartwig is a thoracic surgeon with a clinical focus in robotic assisted minimally invasive thoracic surgery for the treatment of diseases of the chest. He serves as the Surgical Director of the Esophageal Center at Duke. He is also the Director of the Minimally Invasive Thoracic Surgery Fellowship at Duke, while providing advanced instruction in robotic surgery to surgeons around the world. He also leads a successful program of clinical, basic and translational research in thoracic surgery and lung transplantation. He currently directs the Duke Ex Vivo Organ Laboratory (DEVOL), is the Chief of Lung Transplant Research, and is a faculty member at the Duke Clinical Research Institute (DCRI). John L.R. ForsytheJohn L.R. ForsytheProfessor John Forsythe was first appointed as a Consultant Transplant Surgeon at the Royal Infirmary of Edinburgh, UK in 1995. Prior to this, he was a Consultant Surgeon with special interest in renal transplantation at the Royal Victoria Infirmary, Newcastle upon Tyne, UK. He is currently an Organ Utilisation Consultant for NHSBT, working with all departments of health for the UK. Professor Forsythe has held many professional committee appointments, among them Lead Clinician for Organ Donation and Transplantation in Scotland, Chairman of the Scottish Donation and Transplant Group and Chairman of the Safety of Blood, Tissues and Organs Advisory Committee to all four UK health ministers. He is a Past President of the British Transplantation Society and remains Honorary President of the British Society for Histocompatibility and Immunogenetics. Shunji NagaiShunji NagaiDr. Shunji Nagai is a general surgeon in Detroit, Michigan and is affiliated with Henry Ford Hospital. He received his medical degree from Nagoya University- School of Medicine and has been in practice for more than 20 years.

Consent or no objection. The current knowledge on the declaration of will and applicable legal provisions in the field of organ transplantation in Poland

The term “transplantation” is taken from Latin. “transplantare” – which means „vaccinate”,„exaggerate” and it is understood as the procedure of transferring tissue cellsor organs within one organism or between several organisms. An organ donor can bea living person (ex vivo donation) or a deceased person (ex mortuo donation).Organ transplantation is the only recognized treatment for end-stage organ failure.Depending on the type of organ donor, the following types of transplants are distinguished:transplant from a deceased donor and transplantation of the so-called family,i.e. from a living donor, but in this case only one kidney or a fragment of the liverin the case of a pediatric recipient can be transplanted. In the case of retrieving organsfrom a deceased donor, at the moment the patient is declared dead, at the momentof the commission’s confirmation of individual death, the main purpose of further carefor the potential deceased donor is to ensure the proper function of the organs that maybe the subject of transplantation, provided that the organ collection has been verified,i.e. it has been verified whether the deceased did not refuse to organ donation.

Organ transplantation in Romania: challenges and perspectives.

The interest in the field of organ transplantation and the first attempts at making experimental transplant interventions in Romania date from the very beginning of the 20th century. Nevertheless, the evolution of the donating activity and of organ transplantation in Romania has been confronted with a certain inconsistency and a lack of resources necessary to the development of the system. The aim of this study is to analyze the dynamics of the transplantation activity in Romania between 2000 and 2020. The study was accomplished through the analysis of available data corresponding to the above-mentioned period, which were published in the database of the National Transplant Agency, Eurostat and the Global Observatory on Donation and Transplantation. The data were processed using the MedCalc Statistical Software, version 14.8.1 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2014). The activity of donation and organ transplantation in Romania has been maintained at a low level, with a rate of 3.44 donators pmp and a transplantation rate of 12.55 pmp, as reported for the year 2020. Romania remains at a transplantation rate of under 6.6 pmp, despite the considerable increase in the number of patients on the waiting lists, a fact which describes the picture of a relatively weak system, incapable of providing surgical interventions to cover the minimum needs that emerge within a calendar year. Our study points to the fact that the transplantation system in Romania is confronted with a major deadlock. Romania holds the last-but-one place in the ranking of countries in the European Union on transplant activity. The major impediment is the donation rate, which continues to be way below the European average, in a society where the awareness of the necessity to donate is very low, bureaucracy is cumbersome and there is a high degree of mistrust in the medical system, where the equipment is lacking and the infrastructure is incapable of providing services adapted to the modern standards.

Ventriculoureteral shunt: Narrative review of contemporary cases and its historical role in the development of renal transplantation.

Ventriculo-ureteral (VU) shunting is a little-known method of managing hydrocephalus. This paper reviews contemporary uses of this shunting technique and describes its historical significance to the field of organ transplantation. The ureter may serve as a possible backup, or alternative, distal drainage site compared to the more common peritoneum, atrium, and pleural space. Sporadic contemporary uses of the VU shunt have been reported in unique situations, demonstrating a possible utility in modern neurosurgery. Interestingly, the VU shunt played an important role in the development of kidney transplantation. In the late 1940s and early 1950s, David Hume, a general surgery resident, and colleagues at the PBBH undertook a series of human kidney transplantations. Concurrently, Donald Matson, a pediatric neurosurgeon at Peter Bent Brigham, was utilizing the VU shunt in hydrocephalic patients. Dr. Matson's VU shunt technique involved total nephrectomy, and some of the kidneys harvested from Dr. Matson's were used by his general surgery colleagues in their transplantation trials. Although none of the transplanted kidneys from this series were successful, the transplant team in Boston, minus David Hume, went on to perform the world's first kidney transplant a few years later. This relatively unfamiliar procedure may be applicable to specific situations, and it is of historical importance to the field of transplantation.

Implementation of Blockchain Technology Could Increase Equity and Transparency in Organ Transplantation: A Narrative Review of an Emergent Tool.

In the last few years, innovative technology and health care digitalization played a major role in all medical fields and a great effort worldwide to manage this large amount of data, in terms of security and digital privacy has been made by different national health systems. Blockchain technology, a peer-to-peer distributed database without centralized authority, initially applied to Bitcoin protocol, soon gained popularity, thanks to its distributed immutable nature in several non-medical fields. Therefore, the aim of the present review (PROSPERO N° CRD42022316661) is to establish a putative future role of blockchain and distribution ledger technology (DLT) in the organ transplantation field and its role to overcome inequalities. Preoperative assessment of the deceased donor, supranational crossover programs with the international waitlist databases, and reduction of black-market donations and counterfeit drugs are some of the possible applications of DLT, thanks to its distributed, efficient, secure, trackable, and immutable nature to reduce inequalities and discrimination.

Vision and mission of the new Editor-In-Chief

Vision and mission of the new Editor-In-Chief