Use Of Animal Organs Research Articles

Barriers toward xenotransplantation in Arab World.

Organ transplant is a crucial therapeutic strategy offering a life-saving and transformative medical intervention. It provides an opportunity to improve their quality of life and increase their lifespan. The shortage of organs remains a critical global challenge, leading to a prolonged waiting times for organ receivers, which contributes to an increase in morbidity and mortality rates. Hence, xenotransplantation offered a promising solution to the global shortage of organs through the use of animal organs, leading to an increase in donor availability, reducing waiting times, minimizing organ trafficking, improving genetic engineering advancements, and driving scientific innovation. Even though xenotransplantation has many benefits in the clinical setting, it has many barriers that are hindering its achievements and constraining its occurrence. Some barriers to xenotransplant are general, such as the immunological barrier, while others are specific to certain regions due to local causes. The Arab region exhibits disparities in clinical settings compared to the global context, marked by the huge economic crisis and a shortage of trained healthcare professionals. Considering the huge resources and advancements needed in the field of xenotransplantation, this review aims to explore the specific barriers toward xenotransplantation in the Arab countries, highlighting the challenges to overcome these barriers.

The view of the three monotheistic religions toward xenotransplantation.

Xenotransplantation, transplanting animal organs into humans, may offer a solution to the shortage of organs for transplantation. This would increase the chances for scheduled, elective transplantation, even for patients currently ineligible for receiving a human organ. However, xenotransplantation raises specific ethical and philosophical issues, that is, a personal identification of the body parts with the soul and spirit, the relationships between humans and animals, and challenges related to issues of medical and social ethics. The three monotheistic religions have laws and perspectives pertaining to xenotransplantation. This scholarly review examines the theology and viewpoints of the three monotheistic religions and their concerns regarding xenotransplantation (interspecies) in terms of religious-legal rulings, the ethical considerations related to the procedure, through religious scriptures and rulings of scholars of the three faith communities. This review should be viewed as a continuation of an extensive investigation of these issues, as the field of transplantation advances toward clinical trials. It was found that there are no fundamental religious reasons presented by any of the three religions to prohibit the use of animal organs as a means of treating severe and life-threatening conditions. However, there are certain limitations prescribed by each religion relating to the treatment of the animals and the choice of organs to be transplanted.

Organ xenotransplantation acceptance in veterinary students: A multicentric opinion study in Spain.

The shortage of available transplant organs has made it necessary to search for alternatives, one of which is xenotransplantation. However, the use of animal organs could face rejection from society and the personnel involved in its implementation. (a) to analyze the attitudes of Veterinary Degree students in six Spanish Universities towards xenotransplantation; and (b) to determine the factors that affect its acceptance. Of the 2815 students surveyed in the degree program, 2683 valid surveys were obtained. Attitudes towards organ xenotransplantation were evaluated using a validated questionnaire of organ donation. If xenotransplantation was confirmed as a clinical reality, 93% (n=2493) of those surveyed would accept a xenotransplanted organ, whilst 7% would not. If the results of xenotransplantation were worse than those obtained with human donors and it entailed more risk, 12% (n=318) would be in favor. 56% (n=1497) of the students would accept a xenotransplantation provisionally pending the arrival of a human organ. Attitudes towards xenotransplantation were affected by the academic year in which a student was studying, with more favorable attitudes among students in the last year (88% in first year vs. 95% in fifth year; p<.001). More favorable attitudes are also observed depending on the attitude they have towards organ transplantation, with those students being more in favor of donating their organs when they die (94% vs. 88%; p<.001). Veterinary students would have a very favorable attitude toward xenotransplantation if these animal organs functioned as well as human organs. Therefore, these students could play an important role in the future promotion of this technique.

Ethical issues of xenotransplantation in the aspect of religious views

Transplantation allows us to confidently save the lives of previously doomed patients. Unfortunately, this colossal achievement of human progress has a problematic side – the shortage of donor organs. The use of animal organs could solve it. Currently, the issues of xenotransplantation have become relevant again after the experimental xenotransplantation of the kidney of a genetically modified pig in 2021, and the xenotransplantation of the heart in 2022. This practice raises a number of ethical questions. Is it ethical to put humanity at risk by saving one person? Is it ethical to limit the civil rights of a xeno-recipient? Will xenotransplantation create another reason for discrimination? Can the creation of xenochimeras be considered an unacceptable interference in the Divine plan from a religious point of view? Is it ethical to use higher animals for xenotransplantation? Will an increase in the number of xenotransplants create a risk of the identity of the human race? Will xenotransplantation create new questions about equitable organ allocation? The sources of scholars of theologians related to the main Abrahamic religions on this topic are analyzed. Consideration of theological approaches to the new ethical problems presented by xenotransplantation does not allow us to find a unanimity of opinion. However, as this new branch of medical science makes concrete clinical progress, the attitude of society, religious leaders and ordinary believers towards it will improve. From an individual point of view, Judaism does not object to xenotransplantation to prolong and save human life, even in the case of non-kosher animals with genetic modifications. The preservation of life outweighs other values almost without exception. Xenotransplantation, even from a pig, is hailed as a life-sustaining medical intervention from a Jewish ethical perspective by most authors. In Christianity, the motivation is to try to follow the example of Jesus Christ in bringing healing to all those in need. While physiological healing is important, the ultimate goal is the overall well-being of the individual, which requires spiritual, mental, and social well-being in addition to physical health. The most correct generalization about Islamic bioethical views on xenotransplantation would be that, given the state of science, the final ethical and legal definition remains ambiguous, but in general, xenotransplantation as a means of saving human life may be acceptable.

Ethical rejections of xenotransplantation? The potential and challenges of using human-pig chimeras to create organs for transplantation.

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

Determination of the copy numbers of type A porcine endogenous retroviruses in domestic pigs and wild boars

Modern transplantology is in need of transplants. To solve this problem, the use of animal organs and tissues for grafting to humans (xenografts) has been proposed. However, the progress in this direction is hampered by the risk of zoogenous infection of recipients. With regard to economic and ethical criteria and to the anatomical and physiological similarity to humans, the pig is the best source of xenografts. The pig genome harbors type A porcine endogenous retroviruses (PERV), which can infect human cell lines in vitro. A population of Siberian minipigs was raised at the Institute of Cytology and Genetics just for xenografting. The goal of the present study is to analyze the copy numbers of PERV A in Siberian minipigs, their founder breeds Landrace and Large White, and wild boars. The copy numbers of PERVs have been determined by absolute measurement with SYBR Green dye. End-point dilutions of a sample with a known copy number have been used for reference. The PERV A copy numbers in standard samples of Siberian minipig DNA are 2.4, 3.6, and 4.9 per cell, which is consistent with data obtained by other scientists. Minipigs and wild boars show a significant difference in retrovirus copy numbers. Thus, the Siberian minipig genome has a considerable number of type A PERVs, conceivably pathogenic to humans. It is necessary to select animals with minimum PERV numbers in the genome for xenografting. The method of PERV A quantitation with SYBR Green allows detection of such animals and selection of Siberian minipigs for reduction of this index.

The use of animal tissues alongside human tissue: Cultural and ethical considerations.

Teaching and research facilities often use cadaveric material alongside animal tissues, although there appear to be differences in the way we handle, treat, and dispose of human cadaveric material compared to animal tissue. This study sought to analyze cultural and ethical considerations and provides policy recommendations on the use of animal tissues alongside human tissue. The status of human and animal remains and the respect because of human and animal tissues were compared and analyzed from ethical, legal, and cultural perspectives. The use of animal organs and tissues is carried out within the context of understanding human anatomy and function. Consequently, the interests of human donors are to be pre-eminent in any policies that are enunciated, so that if any donors find the presence of animal remains unacceptable, the latter should not be employed. The major differences appear to lie in differences in our perceptions of their respective intrinsic and instrumental values. Animals are considered to have lesser intrinsic value and greater instrumental value than humans. These differences stem from the role played by culture and ethical considerations, and are manifested in the resulting legal frameworks. In light of this discussion, six policy recommendations are proposed, encompassing the nature of consent, respect for animal tissues as well as human remains, and appropriate separation of both sets of tissues in preparation and display.

Are Veterinary Students in Favour of Xenotransplantation? Comparative Opinion Study in a Brazilian and a Spanish University

BackgroundThe shortage of organs has made it necessary to search for new alternatives such as xenotransplantation. However, the use of animal organs could be opposed by society and the personnel involved in its implementation. This study aimed to analyze the attitude of veterinary degree students in a Brazilian university towards xenotransplantation, to determine factors that affect its acceptance, and to compare the attitudes among a control group of veterinary degree students in a Spanish university. MethodsOf the 422 students registered for a veterinary course from 2010 to 2011, 374 were surveyed with a questionnaire completion rate of 89%. Attitudes were evaluated using a validated questionnaire that was self-administered administered anonymously. The process was coordinated by an independent health care worker. We applied the student t and the chi-squared-tests for statistical analysis. ResultsIf xenotransplantation was confirmed as a clinical reality, 90% (n = 338) of Brazilian students would accept the use of a xenotransplanted organ; 94% (n = 350), tissue; and 97% (n = 360), cell xenotransplantation. Attitudes toward xenotransplantation were not determined by the academic year, any psychosocial variable, or attitudes toward deceased human organ donation (P = .167). However, the attitudes would be affected by a belief that the transplanted animal organ would not change anything (P = .001). Interaction with other people was also related to more favorable attitudes (P = .015). Subjects who expressed a more favorable attitude tended to more readily accept cell (P = .000) or tissue xenotransplantation (P = .000). In Spain (control group), the results were similar: 91% (n = 436) would accept a xenotransplantation; 95% (n = 457) tissue; and 97% (n = 467), cell xenotransplantation. Also, this attitude was not affected by the academic year, any psychosocial variable, or attitude toward organ donation (P = .779). ConclusionBoth Brazilian and Spanish veterinary students had favorable attitudes toward xenotransplantation.

Proteomic analysis of liver in miniature pigs according to developmental stages using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry

Due to the shortage of human organ donors for transplant, various studies of xenotransplantation, or the use of animal organs instead of human organs, have been carried out. The organs of porcine are thought to be safer and of a more suitable size for xenotransplantationthan those of nonhuman primates. Understanding the levels of expression of proteins, and their post-translational regulation, would be very practical between different species and among developing stages, though the molecular profiling for xenotransplantation has been rarely studied for porcine, while that of human and rodent is well known. Here, in this present study, we report protein regulation of the developing stages of liver (4-day old neonate, 19-day old piglet and 14-month old adult miniature pigs) using 2-DE and MALDI-TOF. From images of the three different stages, a total of 8 spotswhich were differently regulated were identified, and 5 spots were identified with MALDI-TOF MS. The data presented within this study provides critical direction relating to the development of livers of miniature pigs, which will assist future proteome analysis of the liver, and advance our understanding of the hurdles facing xenotransplantaion.

The Porcine Aortic Tissue Culture System in vitro for Stem Cell Research

Due to the shortage of human donors for transplantation, the use of animal organs for xenotransplantation has come into great interest. Xeno-derived vessels and cardiac valves would be possible alternatives for the patient suffering from cardiovascular diseases. Therefore, we established in vitro culture system of a porcine vessel that could be helpful for the research of xenograft and stem cell research. We primarily isolated porcine thoracic aorta, cultured square-shaped pieces up to 17 days and analyzed its morphology and characters. The endothelial cells were primarily isolated from cultured porcine aortic pieces and their morphology, function and character were analyzed in order to confirm them as endothelial cells at day 3, 4, 8, 10 and 17. Even at day 17, the morphology exhibited the intact endothelial layer as well as specifically expressed CD31 and von Willebrand factor. The morphology of primarily isolated cells from cultured tissues was identical as an endothelial cell. By flow cytometry analysis, more than 80% of the isolated cells expressed CD31 and up to 80% took up acetyl low density lipoprotein (ac-LDL) until day 10 of tissue culture period even though it decreased to about 50% at day 17 that means they not only showed typical endothelial cell characters but also functioned properly. We successfully established and optimized a porcine vascular tissue in vitro culture system that could be a valuable model for in vitro study of xenotransplantation and stem cell research.

Linking organ donors and the medical/scientific research community: a US perspective

The International Institute for the Advancement of Medicine (IIAM) provides non-transplantable organs and tissues for medical and scientific research, education, and drug & device development. The benefits of using human organs and tissues for research are vast, and donating for research provides donor families with a valuable option if their loved one's organs are unsuitable for transplantation. The use of these organs and tissues enables the faster development of more efficacious drugs with improved safety profiles, and enhanced understanding of basic disease processes that directly affect humans. Human organs and tissues offer unique advantages over the use of animal organs and tissues as it is human diseases and conditions which we seek to treat, and so logically the results can be more directly applied. The added advantage of accessing non-transplantable, human organs is that they are in superb condition, and so experiments can be conducted in a very physiologically-relevant system. Although the US is a sizeable country with a large population and individual regulations governing human tissue collection and usage for each of the 50 states comprising the US this article will discuss how IIAM succeeds in immediately linking organ donors and qualified researchers, ultimately to the great benefit of patients.

Are Veterinary Students in Favor of Xenotransplantation? An Opinion Study in a Spanish University With a Xenotransplantation Program

Background The shortage of available transplant organs has made it necessary to search for new alternatives, one of which is xenotransplantation. However, the use of animal organs and the personnel involved in its implementation could face opposition. Our objective was to analyze the attitudes of veterinary degree students in a Spanish university toward xenotransplantation and to determine the factors that affect its acceptance. Methods Of the 515 students registered in a veterinary degree course (2007–2008), we surveyed 482 94% of whom completed the questionnaire. Attitudes toward organ xenotransplantation were evaluated using a validated, self-administered questionnaire concerning organ donation, which was completed anonymously. We applied Student's t-tests and χ 2 tests. Results If xenotransplantation was confirmed as a clinical reality, 91% ( n = 436) of those students surveyed would accept a xenotransplanted organ, whereas 9% ( n = 46) would not. Furthermore, 95% ( n = 457) would accept tissue xenotransplantation and 97% ( n = 467) cell xenotransplantation. Attitudes toward xenotransplantation were not affected by the academic year in which a student was studying, even when this was the year in which it was taught as a subject. Attitudes were not associated with any pyschosocial variable or attitude toward deceased organ donation; ( P = .779). The students who believed that the demand for organs is not covered had a more favorable attitude toward xenotransplantation than those who think that there is no shortage (91% vs 70%; P = .027). Conclusion Veterinary students had favorable attitudes toward xenotransplantation, assuming that the animal organs functioned as well as human organs. Therefore, these students could play important roles in the future promotion of this technique.

Population Study about the Attitude toward Organ Xenotransplantation in the Population from Eastern Europe Resident in Southeast Spain

The objective of this paper is to analyze the attitude toward xenotransplantation and to determine the variables that influence this attitude in the population of southeast Spain who were born in Eastern European countries. A random sample was taken of natives from Eastern Europe residing in southeast Spain (n=320). The sample was obtained randomly between November 2005 and April 2006 and stratified according to the respondents' nationality. Attitude was evaluated using a validated questionnaire which was self-administered and completed anonymously. The control group was a random sample of the native Spanish population (n=250). The statistical analysis used included Student's t-test, the chi-square test, Fisher's exact test, and a logistic regression analysis. The questionnaire completion rate was 83% (n=267). Regarding the use of animal organs for transplantation in humans, if the outcome were similar to that achieved when using human organs, 43% (n=114) would be in favor, 32% (n=86) undecided, and the remaining 25% (n=67) would be against it. This attitude is less favorable than in the control group (43% versus 74%, p<0.001). The attitude was related to the following factors: 1) the country of origin (p<0.001); 2) participation in social help activities (p<0.001); 3) discussion on organ donation and transplantation within the family (p=0.005); 4) previous experience of organ donation and transplantation (p=0.002); 5) the respondent's religion (p=0.002); 6) knowing that one's partner had a favorable attitude toward transplantation (p<0.001); 7) the respondent's belief that he or she might need a transplant in the future (p<0.001); 8) the attitude toward human donation, both from cadaver (p<0.001) and living (p<0.001) donors. The following were also independent variables in the subsequent multivariate analysis: 1) favorable attitude toward cadaver organ donation (OR=4.998); 2) previous experience of donation (0R=2.857); 3) partner's attitude against transplantation (OR=0.079); and 4) attitude toward living donation (OR=12. 703). The attitude toward xenotransplantation is less positive among Eastern Europeans living in Spain than in the native Spanish population and is influenced by many psychosocial factors that are mainly related to human organ donation.

Clinical Trials of Xenotransplantation: Waiver of the Right to Withdraw from a Clinical Trial Should Be Required

Xenotransplantation pits clinical research ethics against public health needs because recipients must undergo long-term, perhaps life-long, surveillance for infectious diseases. This surveillance requirement is effectively an abrogation of the right to withdraw from a clinical trial. Ulysses contracts, which are advance directives for future care, may be an ethical mechanism by which to balance public health needs against limitation of individual rights.

Education is key to controlling visceral leishmaniasis

Education is key to controlling visceral leishmaniasis

Attitudes of Primary Care Professionals in Spain Toward Xenotransplantation

Objective The deficit in transplantable organs is making it necessary to find alternative sources. One possibility is xenotransplantation. However, the use of animal organs may be rejected by society and among health professionals. Primary Care is fundamental for promoting matters of health; in Spain it has access to nearly 100% of the population. Our objective was to analyze the acceptance of this therapy, although it is experimental, among Primary Care professionals, given that they are the ones most involved in spreading information about this therapy if it was confirmed to be useful. Materials and Methods A random sample was stratified by sex, job category, and geographical location among Primary Care personnel, including 428 professionals in 32 health centers among population of 2851 professionals. Attitudes toward xenotransplantation were evaluated using a questionnaire on psychosocial attitudes validated in our geographical area. Contact was made in each center with the Doctor Coordinator for doctors, the Nursing Coordinator for nurses, and an Administrative Officer for ancillary personnel. The chi-square test and Student t test were applied to evaluate categorical and continuous data, respectively. Results Attitudes toward xenotransplantation were similar to those obtained in human organs: favorable in 79% (n = 325), whereas 19% (n = 78) had doubts and 2% (n = 10) were against. The attitude was more favorable in men (89% vs 72%; P < .000), those who had cared for transplant patients (84% vs 71%; P = .009), those with previous experience in organ donation and transplantation (84% vs 75%; P = .033), those with an attitude in favor of cadaveric organ donation (83% vs 66%; P < .0001), and those in favor of living donation of the kidney ( P < .000) or the liver ( P < .000), as well as those who believed that they may need a transplant at some time in the future (84% vs 74%; P = .045). There was a clear difference in attitude according to job category ( P = .018): approval rates were 89% for doctors, 76% for nurses, and 70% for ancillary personnel. Conclusions Attitudes toward future application of xenotransplantation were quite positive among doctors. However, the attitudes of nursing and ancillary personnel were similar to those of the general population. The main factors related to such an attitude depended mainly on the previous relationship and attitude of the respondent toward human organ donation and transplantation.

Attitude Toward Xenotransplantation Among Residents

Introduction The deficit in transplant organs has made it necessary to search for alternatives, among them research into xenotransplantation. However, the use of animal organs may cause rejection in society and among health professionals. The objective was to analyze the acceptance of this therapy among Residents, given that they would be the professionals most involved in its application if such a therapy proves to be useful. Materials and methods A random sample stratified by the services of the Residents in a third-level hospital with an organ transplant program and accredited for teaching at undergraduate and postgraduate levels ( n = 171). The attitude toward xenotransplantation was evaluated using a questionnaire that analyzes different pychosocial variables that may influence such attitude. 5 Results The sample consisted of 171 residents (mean age 28 ± 4 years; 56% women). Attitudes toward xenotransplantation, whether the results were similar to those obtained with human organs, were positive in 81% ( n = 138) of cases, with 16% ( n = 27) having doubts and 3% ( n = 6) being against. The attitude was more favorable among residents in favor of cadaveric donation (83% vs 57%; P < .05) and of living donation either of the kidney (90% vs 55%; P < .001) or of the liver (88% vs 56%; P < .001), and among those who consider that they might need a transplant at a given point in the future (88% vs 73%; P < .05). Conclusion Residents have a positive attitude toward the application of a possible xenotransplantation in safe conditions similar to those that currently exist in human organ donation. Such a favorable attitude was greatly influenced by a positive attitude toward human organ donation, in cadaveric as well as in living donation, and when considering oneself to be a possible candidate for a transplant.

Life-supporting pig-to-baboon renal transplantation using GalT knockout donors: Benefit of cotransplanting a vascularized donor thymic graft

The use of animal organs for human transplantation could potentially alleviate the worldwide critical shortage of donor organs, and thus has stimulated investigation of novel strategies directed at making xenotransplantation applicable to the clinic. The latter will likely require overcoming barriers of rejection through strategies utilizing either immune suppression or tolerance induction, or a combination of the two. We have previously reported that vascularized donor thymic tissue grafts, transplanted either as composite thymokidneys or vascularized thymic lobe grafts, induced tolerance across fully allogeneic barriers in miniature swine. Recently, we have applied the strategy of vascularized thymic lobe transplantation in a model of hDAF pig-to-baboon xenotransplantation and demonstrated that these grafts induced donor-specific unresponsiveness for up to 2 to 3 months following transplantation, at which time the grafts were lost from apparent humoral rejection. We have now extended these studies using cloned α-1,3-galactosyltransferase (GalT) knockout pigs as donors. We report here our initial experience in a preclinical model of pig-to-baboon xenotransplantation. This abstract presents clinical data on recipients of GalT knockout kidneys, especially focusing on four long-term recipients of GalT knockout kidney plus thymus transplantation in detail. Briefly, these four baboons receiving either xeno-thymokidneys or vascularized thymic lobe plus kidney maintained longer than 2 months. Three of four long-term survivors maintained normal plasma creatinine levels for 56, 68, and 83 days, respectively, before expiring from unexpected causes (anesthetic complication during surgery to replace an infected intravenous catheter (day 68), and myocardial infarction, possibly drug-induced on days 56 and an arterial catheter trouble on day 83. Cytotoxic T-lymphocyte assays on day 78 in one long-term acceptor showed that the baboon maintained anti-allo cytotoxic T-lymphocyte responses but lost antipig cyctotoxic T-lymphocyte responses, indicating donor-specific unresponsiveness. The fourth baboon experienced an apparent rejection crisis between days 53 and 65, which reversed with anti-T-cell rejection therapy; subsequently the animal expired on day 81 from pneumonia. Neither hyperacute nor accelerated acute rejection was observed in any animal. Use of GalT knockout donors markedly extends the survival of vascularized thymus plus renal xenografts in baboons. Although the induction regimen still needs to be modified to reduce complications, these initial results are encouraging with regard to the potential of cotransplanting vascularized thymic tissue with organ xenografts as a means of achieving long-term tolerance across pig-to-primate barriers.

Beyond Antibody-Mediated Rejection: Hyperacute Lung Rejection as a Paradigm for Dysregulated Inflammation

The use of animal organs for transplantation in humans is seen as a potential solution to the short supply of human donor organs available for clinical transplantation. However, to develop this therapeutic option as clinical reality will require surmounting formidable obstacles. The primary immunologic barrier to pig-to-human xenotransplantation is hyperacute rejection (HAR), a phenomenon previously characterized as resulting from antibody binding and complement activation. This article will first review recent progress in the development of specific strategies to overcome hyperacute lung rejection (HALR), through production of genetically engineered pig organs, modification of the host innate immunity and control of antibody and complement. Additional therapeutic targets identified in HALR are reviewed, with particular emphasis on recent studies describing a critical role for the coagulation cascade in HAR.

Marked prolongation of porcine renal xenograft survival in baboons through the use of α1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue

The use of animal organs could potentially alleviate the critical worldwide shortage of donor organs for clinical transplantation. Because of the strong immune response to xenografts, success will probably depend upon new strategies of immune suppression and induction of tolerance. Here we report our initial results using alpha-1,3-galactosyltransferase knockout (GalT-KO) donors and a tolerance induction approach. We have achieved life-supporting pig-to-baboon renal xenograft survivals of up to 83 d with normal creatinine levels.