Transplantation Medicine: An Historical Perspective

In solid organ transplantation, especially renal transplantation, for the induction of immune tolerance, accumulating evidence has revealed that Regulatory B cells (Breg) play a crucial role in stimulating immune tolerance, alleviating immune responses, and improving graft survival. We describe the heterogeneous nature of Bregs, focusing on their defining surface markers and regulatory functions. Meanwhile, the major cytokine secretion function and the correlation between Breg and Treg or other immune checkpoints to balance the immune responses are addressed. Furthermore, we summarized the intrinsic and extrinsic pathways or costimulatory stimuli for the differentiation from naïve B cells. More importantly, we summarized the progression of the immune tolerance induction role of Breg in solid organ (kidney, liver, heart, lung, and islet) transplantation. This is an up-to-date review from the origin of Breg to the function of Breg in solid organ transplantation and how it induces immune tolerance in both murine models and human solid organ transplantation.

Peripheral immunoregulation depends on T regulatory cell trafficking into the allograft to modulate the local alloresponse. Little is known about the relevance of trafficking receptors for Tregs after solid organ transplantation in humans. In this study, expression of the peripheral chemokine receptors CXCR3 and CCR5 on CD4⁺ FOXP3⁺ Treg cells was analysed and correlated with allograft function in renal transplant recipients. Flow cytometry analysis of peripheral blood mononuclear cells of 54 renal transplant recipients receiving a calcineurin inhibitor-based immunosuppression was performed for CD4, CD25, FOXP3, CXCR3 and CCR5 within the first 18 months post-transplantation. Correlation analysis of chemokine receptor expression and glomerular filtration rate as calculated by MDRD (eGFR) was performed. Expression of the peripheral homing receptors CXCR3 (r = 0.44, P < 0.05) and CCR5 (r = 0.45, P < 0.05) on FOXP3⁺ Tregs correlated with renal allograft function (eGFR) in patients receiving tacrolimus (n = 28), but not cyclosporine A (CsA) (n = 26). CsA but not tacrolimus reduced surface expression of CXCR3 on FOXP3⁺ Tregs in renal transplant recipients as correlated to trough levels (r = -0.42, P < 0.05). In contrast to CD4⁺ CXCR3⁺ CD25(lo) T cells, flow-sorted CD4⁺ CXCR3⁺ CD25(hi) Tregs isolated from healthy individuals did not produce IFNγ or IL-17 ex vivo and expressed high levels of GARP mRNA both at baseline as well as after TCR activation indicating functional regulatory activity. Expression of the peripheral trafficking receptors CXCR3 and CCR5 on FOXP3⁺ Tregs is associated with renal allograft function. These results suggest that Treg trafficking may also depend on the interaction of CXCR3 or CCR5 and their respective ligands.

The objective of this dissertation is to first identify if there are any academic research gaps in our understanding of the medical supply chain and secondly to understand the role and impact of logistics on the human organ transplant process. The first essay identifies the current status of medical supply chain literature and provides future direction for improving the medical supply chain. This was accomplished by preforming a systematic literature review and a bibliometric analysis from 2,160 publications was conducted. The second essay explores how logistical aspects impact transplant logistics performance and the quality of life for the transplant recipient. Survey data was collected from medical professionals and analyzed using structural equation modeling. The third essay identifies the factors are influencing the number of donor kidneys discarded each year. A retrospective analysis of all deceased donor kidneys procured in hospitals in UNOS region 4 (Texas and Oklahoma) from January 1, 2001, to June 28, 2021, was conducted. Data was analyzed using multinomial logit regression and panel data analysis. As a result, we identified several medical and logistics factors that have influenced the number of donor kidneys discarded in the United States.

EMBO Reports (2018) 19: e46337[OpenUrl][1][FREE Full Text][2] Gene editing and stem cell biotechnologies are being applied to create chimeric animals with human organs, which could alleviate the current shortage of human organs for transplantation. While the medical benefits of xenotransplantation appear to be significant, we discuss specific ethical, medical, cultural, and financial challenges and potential solutions that need to be addressed before clinical trials using organs from human‐animal chimeras should begin. > The use of animal organs to replace defective organs in human patients dates back at least to 1838 when the first pig‐to‐human corneal transplant was performed. Organ transplantation has a long history. The use of animal organs to replace defective organs in human patients dates back at least to 1838 when the first pig‐to‐human corneal transplant was performed. The first human skin transplant was done in 1869, the first successful kidney transplant between fraternal twins took place in 1954, and the first heart transplant was performed in 1967. Aortic valve replacement with a porcine heart valve was first reported 2 years later in 1969 and continues to be used to this day. Notwithstanding, of the clinical successes, organ transplantation has been held back by a huge shortage of people willing to donate their organs. Currently, more than 115,000 people are organ transplant candidates in the USA; 75,000 of these are on the national organ waiting list (https://optn.transplant.hrsa.gov). About 25% of patients on the list die before an organ becomes available. Xenotransplantation—using organs from animals for transplantation—has great potential to alleviate this organ shortage. However, tissue rejection and infections have greatly limited the effectiveness of cross‐species transplantations. Recent advances in biotechnology, including gene editing and stem cell science, may provide the key elements needed to create animals that grow human organs for transplantation. Research is currently focusing on growing human hearts, … [1]: {openurl}?query=rft.jtitle%253DEMBO%2BReports%26rft_id%253Dinfo%253Adoi%252F10.15252%252Fembr.201846337%26rft_id%253Dinfo%253Apmid%252F29991538%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=embor&resid=19/8/e46337&atom=%2Fembor%2F19%2F8%2Fe46337.atom

Currently, there is a serious shortage of human organs, such as kidneys and corneas, available for transplant to patients who need them. State laws—through the adoption of the Uniform Anatomical Gift Act— support an “altruistic” system of organ donation, in which the supply of transplantable organs depends upon the willingness of individuals to relinquish organs without financial compensation. The author of this Comment, an economist, proposes that state laws should instead support a combined altruistic-market system of organ procurement and distribution. In such a system, not only could individualsgivetheir organs, but those who so desired couldselltheir organs—to be removed and transplanted upon their death, or possibly even during their life in appropriate cases—with the proceeds going to the donor or his estate. The author contends that statutory authorization of a combined altruistic-market system of organ transfer—for which the current mixed voluntary-commercial blood system provides a precedent—would foster the growth of a new incentive (the receipt of money) to relinquish one’s organs for transplantation. The sale of organs could (1) alleviate the organ shortage, (2) decrease the incidence of organ rejection by the host, and (3) lessen the need to remove organs from living donors. The author confronts various practical and ethical objections to the introduction of a commercial market in human organs, and concludes that the objections are unjustified, or can be addressed effectively through appropriate statutory provisions, or are outweighed by the benefits of a vastly increased supply. He calls for support for his proposal from organized medicine, and suggests that the new system be introduced on an experimental basis in a single state prior to nationwide implementation.

ABSTRACT: - We all have been hearing, reading and seeing many issues regarding organ transplantation, but many people are not aware and serious regarding Human organ transplant. Many patients struggle for life after failure of functioning of some major organs. A patient with a case of renal failure can survive for some period with the help of advance technique Viz. Dialysis, but patients with failure of function of liver or Heart etc. have no substitute for Human Organ Transplant. It is a small effort to encourage and create awareness in people to promote organ transplant. In last 10 years people are much aware regarding organ donation and organ transplant. The person certified as brain dead can only donate his healthy organs to a needy and increase his life span [2]. In India we can see advancement in the field of transplantation. The law regarding Human Organ Transplant was passed in the year 1994 it came into force in 1995[1]This law includes Regulations regarding removal, preservation and transplantation of organ for treatment purpose and prevention of commercialization of human organs[1

COVID-19: transplant works toward adaptation.

Integrated Analysis Toolset for Defining and Tracking Alloreactive T-cell Clones After Human Solid Organ and Hematopoietic Stem Cell Transplantation.

Hyperacute rejection (HAR) is the first critical immunological hurdle that must be addressed in order to develop xenogeneic organs for human transplantation. In the area of cell-based xenotransplant therapies, natural antibodies (XNA) and complement have also been considered barriers to successful engraftment. Transgenic expression of human complement inhibitors in donor cells and organs has significantly prolonged the survival of xenografts. However, expression of complement inhibitors without eliminating xenogeneic natural antibody (XNA) reactivity may provide insufficient protection for clinical application. An approach designed to prevent XNA reactivity during HAR is the expression of human alpha1, 2-fucosyltransferase (H-transferase, HT). H-transferase expression modifies the cell surface carbohydrate phenotype of the xenogeneic cell, resulting in the expression of the universal donor O antigen and a concomitant reduction in the expression of the antigenic Galalpha1,3-Gal epitope. We have engineered various transgenic pig lines that express HT in different cells and tissues, including the vascular endothelium. We demonstrate that in two different HT transgenic lines containing two different HT promoter constructs, expression can be differentially regulated in a constitutive and cytokine-inducible manner. The transgenic expression of HT results in a significant reduction in the expression of the Galalpha1,3-Gal epitope, reduced XNA reactivity, and an increased resistance to human serum-mediated cytolysis. Transgenic pigs that express H-transferase promise to become key components for the development of xenogeneic cells and organs for human transplantation.

With rare exceptions, Roman Catholic moral theologians condemn the sale of human organs for transplantation. Yet, such criticism, while rhetorically powerful, often oversimplifies complex issues. Arguments for the prohibition of a market in human organs may, therefore, depend on a single premise, or a cluster of dubious and allied premises, which when examined cannot hold. In what follows, I will examine the ways in which such arguments are configured. For example, Thomas Aquinas' (1224-1274) understandings of embodiment and moral uses of the body are usually interpreted as, and cited in support of, foreclosing a market in human organs. Aquinas' principle of totality requires that one preserve the wholeness of the human body. In approaching Aquinas' texts, I will assume the role of a revisionist who takes seriously his core commitments, while at the same time indicating that one can further develop his understanding of the body in ways which are supportive of the sale of human organs while remaining in conformity with the author's core concerns. Such considerations will provide significant grounds for concluding that a market in human organs for transplantation appreciates the embodied nature of the human person, respects the body and its parts as personal, rather than as mere things, is consistent with acknowledging God's dominion over our lives and bodies, and constitutes an appropriate utilization of God's gifts to us. Moreover, such a market would likely create significant opportunities charitably to help others, to enhance human dignity and to protect against the serious dehumanization of current national bureaucratic procedures for organ donation.

History of transplant organs originates from a series of experimental studies, for which in 1912 Karel Alexis (Alexis Carrel) was awarded the Nobel Prize for pioneering work. Surgical transplantation of human organs from deceased and living donors, the sick and dying patients began its development after the Second World War. Over the past 50 years, transplantation of human organs, tissues and cells began to practice worldwide. Due to managed to save more than one life and improve its quality. The demand has always exceeded supply, despite a significant increase in the scale of organs from deceased donors, as well as an increase in recent years, the use of organs from living donors. Lack of available grafts for transplantation not only contributed to the development in many countries, procedures and systems to increase their numbers, but also stimulated the growth of illicit trade in human organs. Analysis of foreign countries concerning transplantation of organs and human allows to distinguish two models of regulation donation of organs and tissues from deceased persons, so- called presumed and presumption of bad weather. Presumed is also known in the legal literature as alleged or model objections. It applies to those who died, according to her removal and use of organs from deceased performed if the life of the deceased has expressed objection to this, or if not express denial of his relatives or legal representatives. As for the second model, namely the presumption of dissent it means if his death the decedent expressly declared his consent to organ removal or his family members clearly expressed opposition to such action in the case when deceased did not leave such a statement. In such cases, the lack of agreement is considered as a waiver of transplantation. According to this principle, it is assumed that everyone in advance disagrees with the fact that her organs be transplanted to another person. Analysis of social, criminal and medical factors provides a basis for predicting the high level of delinquency in the field of transplantation and significant negative social consequences in this regard. Illegal transplantation always perpetrated regarding the donor or recipient. In violation of the law transplant human organs or provides for criminal responsibility century. 143 of the Criminal Code of Ukraine Violation of law transplant human organs or tissue and Art. 144 of the Criminal Code of Ukraine Violent donation. Preventing crime in the field of transplantation of organs or human is carried out primarily on the factors that cause certain types of crime in the medical practice regarding organ transplantation or human tissue. In scale implementation of preventive activities in the field of transplantation of organs or human implemented at the national level, regional or sectoral level, object level and the individual level.

The aim: To highlight and analyze the international aspect of the legal regulation of human organs and tissues transplantation, as well as foreign experience of regulation in this area within the relevant national legal systems (for example, US, Germany, Israel, Switzerland, Spain, Argentina, China and India). Materials and methods: Methodologically, this work is based on the system of methods, scientific approaches, techniques and principles with the help of which the realization of the research aim is carried out. There have been applied universal, general scientific and special legal methods. Conclusions: Thus, the efforts of the international community and the countries under study in the field of transplantation are focused on a wide range of important issues that need to be regulated. The international legal regulation of transplantation covers the results of the activities of such international organizations as the World Health Organization, the Council of Europe, and the World Medical Assembly. The acts adopted by them are mainly of a recommendatory nature (with the exception of some Council of Europe acts on trafficking in human organs) and are addressed primarily to States, offering guidelines and standards for the legal regulation of transplantation within national legal orders. Therefore, the issues of donation and transplantation of human organs and tissues in the respective states are determined by special legislative acts, which comprehensively regulate the procedure for their transplantation.

The legal regulation of organ transplantation in Azerbaijan is currently in an active phase of development, seeking to balance the significant life-saving potential of transplants with the need for robust ethical standards and effective criminal law safeguards.This article provides a comprehensive analysis of the Azerbaijani legal framework governing organ donation and transplantation, with particular emphasis on the criminal law provisions addressing illegal organ trade and unlawful transplantation practices.The paper traces the evolution of relevant national legislation, beginning with the 1999 Law on Human Organ and (or) Tissue Transplantation and culminating in the adoption of the new Law on Donation and Transplantation of Human Organs and (or) Tissues in 2020.Attention is given to key articles of the Criminal Code that establish liability for offenses such as coercive organ removal, the commercial sale of organs, and trafficking in human beings for the purpose of organ harvesting.The article also explores law enforcement and judicial practice through the lens of documented cases of illegal transplantation and organ trafficking in Azerbaijan, emphasizing the main difficulties faced in identifying such crimes and bringing perpetrators to justice.In addition, a comparative analysis is conducted to assess the extent to which Azerbaijan's legal framework aligns with international standards, including the World Health Organization's Guiding Principles on Human Cell, Tissue and Organ Transplantation and the relevant conventions of the Council of Europe.Particular focus is placed on the principles of voluntary and informed consent, the absolute prohibition of organ commercialism, the severity of legal sanctions, and the role of international cooperation mechanisms.The study concludes that although Azerbaijani law formally prohibits illegal organ trade and includes penalties that reflect global legal standards, there remain persistent challenges related to law enforcement capacity, public awareness, and the underdevelopment of cadaveric donation systems.

Vitamin D may act as an immune modulator in experimental and human organ transplantation, but these data are yet to be confirmed in human liver transplantation (LT). This study aimed to assess the relationship between acute liver allograft cellular rejection (ACR) and pretransplant serum vitamin D concentration or post-transplant vitamin D supplementation. We studied 133 LT recipients who underwent two per protocol allograft biopsies in the early post-operative period, plus on-demand biopsies as clinically indicated. ACR estimate was given according to the Banff scheme in biopsies obtained along two follow-up periods: (a) from the transplant operation to the end of the second month (0-2 months); (b) and from the third month to the end of the eighth month (3-8 months) post-LT. The median pretransplant serum 25-hydroxyvitamin D concentration was 12.5 ng/ml; 40 patients had concentrations < or =12.5 ng/ml, of whom six had < or =5.0 ng/ml. Seventy-nine recipients received oral vitamin D(3) supplementation to treat post-transplant osteoporosis. In the 0-2 months period, moderate-to-severe rejection episodes were independently associated with cytomegalovirus reactivation (P<0.005) and progressively lower pretransplant serum 25-hydroxyvitamin D concentrations (P<0.02). Early vitamin D(3) supplementation was independently associated with a lack of ACR (P<0.05). These results suggest that vitamin D may favour immune tolerance towards the liver allograft.

Immunocompromised patients are traveling at increasing rates. Physicians caring for these complex patients must be knowledgeable in pretravel consultation and recognize when referral to an infectious disease specialist is warranted. This article outlines disease prevention associated with international travel for adults with human immunodeficiency virus, asplenia, solid organ and hematopoietic transplantation, and other immunosuppressed states. While rates of infection may not differ significantly between healthy and immunocompromised travelers, the latter are at greater risk for severe disease. A thorough assessment of these risks can ensure safe and healthy travel. The travel practitioners’ goal should be to provide comprehensive risk information and recommend appropriate vaccinations or prevention measures tailored to each patient’s condition. In some instances, live vaccines and prophylactic medications may be contraindicated.