Understanding of and attitudes to xenotransplantation: a survey among Italian university students

Xenotransplantation is currently at the experimental stages on animal models and many problems still have to be overcome in the biomedical, immunological and ethical fields. Moreover, people's attitudes to xenotransplantation vary: surveys among intensive-care staff have revealed negative opinions, while the general public and students seem to be more positive. Little is known about the influence of schooling and the choice of university faculty on attitudes to xenotransplantation. The aims of this study were: (i) to evaluate university students' attitudes to xenotransplantation; (ii) to investigate any socio-demographic, religious and educational determinants behind students' opinions on xenotransplantation. University undergraduates on five different courses were surveyed at Padua University. A 24-item questionnaire was distributed to students at the end of lectures and completed anonymously immediately after its distribution. No information was given to students beforehand. Statistical analysis: chi-squared, Pearson's test; P-values <0.05 were considered significant. A total of 585 of 602 (97.2%) students completed the questionnaire (132 males, 453 females, mean age 20.4, range 19 to 43 yr). They were on courses in Medicine (33.85%), Agriculture (5.98%), Veterinary Medicine (11.45%), Psychology (18.46%) and Educational Sciences (30.26%). As for their previous schooling, they came from classical or scientific high school (58.3%), technical college (14.7%), language college (6.3%), teacher training college (11.9%) or others (8.8%). Concerning their religious beliefs, 83% were Catholics, and 56.2% defined themselves as practising Catholics. Eighty-eight percentage of the students knew of the possibility of animal organs being transplanted into humans and 77.9% of them approved of this idea. When grouped according to gender and education, a higher proportion of students approving of xenotransplantation were male (P = 0.017) and had attended classical or scientific high school (P = 0.011). Disapproval for moral, ethical or religious reasons was higher among practising than among non-practising Catholics; the latter rejected xenotransplantation more for immunological and infectious reasons (P = 0.014). As for the type of university course, a higher proportion of students approving of xenotransplantation attended science courses (Veterinary Medicine, Agriculture and Medicine vs. Educational Sciences and Psychology) (P = 0.013). University students generally approved of xenotransplantation. Male gender and a high-school education were associated with a greater acceptance of xenotransplantation. Practising vs. non-practising Catholics reported significantly different reasons for any disapproval of xenotransplantation. The choice of a science rather than an arts faculty at university was more strongly associated with a positive opinion on xenotransplantation.     

The ethics of organ donation,donation after circulatory determination of death,and xenotransplantation from an Islamic perspective

Donation after circulatory determination of death (DCDD) and xenotransplantation are advanced as possible solutions to the growing gap between the number of individuals in need of organ transplantation and the pool of donors. Investigating how various publics, including religious leaders, might view these “therapies” is essential for broad public and professional support and will be needed in order to make these solutions viable. This study, therefore, presents normative Islamic bioethical perspectives on donation after circulatory determination of death and xenotransplantation. First, we will discuss foundational Islamic ethico‐legal debates regarding organ donation. These debates can be grouped into three broad positions, those who consider organ donation categorically impermissible as a violation of human dignity (?urma and karāma ), those who agree that organ donation is impermissible in principle, but allow it conditionally on the basis of dire necessity (?arūra ), and those who permit organ donation based on notions of public interest (ma?la?a ). Next, we will reflect upon the additional ethical dimensions DCDD and xenotransplantation add to these debates. We contend that the condition of minimal harm to the donor and the definition of death need to be accounted for within Islamic perspectives on DCDD. Xenotransplantation, on the other hand, highlights concerns about using pigs for therapeutic purposes. We conclude by commenting on additional questions that remain to be addressed in the Islamic bioethical debate over these practices and with recommendations for further research.     

Xenotransplantation: A historical–ethical account of viewpoints

Formal clinical trials of pig-to-human organ transplant—known asxenotransplantation—may begin this decade, with the first trials likely to consist of either adult renal transplants or pediatric cardiac transplant patients. Xenotransplantation as a systematic scientific study only reaches back to the latter half of the 20th century, with episodic xenotransplantation events occurring prior to that. As the science of xenotransplantation has progressed in the 20th and 21st centuries, the public's knowledge of the potential therapy has also increased. With this, there have been shifting ethical stances toward xenotransplantation in key areas, such as religious and public viewpoints towards xenotransplantation, animal rights, and public health concerns. This review provides a historical–ethical account of xenotransplantation and details if or how viewpoints have shifted over time.     

Executive summary

Abstract:  The International Xenotransplantation Association islet xenotransplantation consensus statement describes the conditions for undertaking clinical trials of porcine islet products in type 1 diabetes. Chapter 1 reviews the key ethical requirements and progress toward the definition of an international regulatory framework for clinical trials of xenotransplantation. Chapters 2 to 7 provide in depth and agreed-upon recommendations on source pigs, pig islet product manufacturing and release testing, preclinical efficacy and complication data required to justify a clinical trial, strategies to prevent transmission of porcine endogenous retrovirus, patient selection for clinical trials, and informed consent. It is planned to update this initial consensus statement in a year's time in light of progress in research, changes in the regulatory framework, and comments submitted after publication.     

Xenotransplantation--ethics and regulation

Healthcare workers, researchers, and policy makers find themselves in challenging times, being required to make (often prompt) decisions in the face of novel ethical dilemmas. Moral theory may assist with decision-making in complex areas of medicine such as the xenotransplantation of insulin-producing cells to reverse diabetes. Moral theory attempts to capture intuitions about whether an action is right or wrong and it may gives us a deeper understanding of moral claims as it gives us an account as to why an action is good or bad. We may opt to choose different ethical frameworks such as consequentialism, principlism or a duty-based approach, to assist with deciding a certain action in a particular scenario. The xenotransplantation of porcine insulin-producing cells is a potential solution to the shortage of human tissue. It is crucial for the advancement of xenotransplantation that the benefits to society outweigh the risks and whilst there is enormous potential to assist mankind, there are unique bioethical challenges and dilemmas. New treatment strategies should be regulated appropriately to minimize risks to patients, their relatives and the wider community. There are specific regulations (such as those developed by the FDA) that provide a robust framework for the safe implementation of xenotransplantation and more generally applicable ones such as the Declaration of Helsinki. Xenotransplantation is either morally acceptable or not to an individual. Patients must ultimately decide as to whether they would accept a certain form of treatment or not, a decision which would take into account their religious beliefs and categorical objections. There is no point in developing a treatment option unless there is good patient support. To that end, a study was conducted to ascertain the acceptance of tissue from different animal sources, by diabetic patients in England and Australia. Interviews were conducted to ensure that patients' views were reflected in their answers. There were 316 English and 195 Australian questionnaire respondents and the vast majority would accept human (85%, 94%), porcine (68%, 85%) or non-human primate (67%, 82%) tissue, respectively. This study suggests that a large proportion of diabetic patients may accept a xenotransplantation product.     

异种移植免疫排斥的研究进展

异种移植是解决人体器官严重短缺的重要思路.随着对异种移植排斥和人畜共患感染性疾病的深入研究,以及α-1,3-半乳糖苷转移酶基因敲除猪的成功构建,以猪为供体的异种移植与临床应用之间的距离正在逐渐缩短.阻碍异种移植发展的主要障碍仍是免疫排斥反应.本文试就目前异种免疫排斥的研究进展进行综述,希望对未来的临床异种移植研究提供参...     

Comparison of hematologic,biochemical, and coagulation parameters in α1,3‐galactosyltransferase gene‐knockout pigs,wild‐type pigs,and four primate species

Ekser B, Bianchi J, Ball S, Iwase H, Walters A, Ezzelarab M, Veroux M, Gridelli B, Wagner R, Ayares D, Cooper DKC. Comparison of hematologic, biochemical, and coagulation parameters in α1,3‐galactosyltransferase gene‐knockout pigs, wild‐type pigs, and four primate species. Xenotransplantation 2012; 19: 342–354. © 2012 John Wiley & Sons A/S. Abstract: Background: The increasing availability of genetically engineered pigs is steadily improving the results of pig organ and cell transplantation in non‐human primates (NHPs). Current techniques offer knockout of pig genes and/or knockin of human genes. Knowledge of normal values of hematologic, biochemical, coagulation, and other parameters in healthy genetically engineered pigs and NHPs is important, particularly following pig organ transplantation in NHPs. Furthermore, information on parameters in various NHP species may prove important in selecting the optimal NHP model for specific studies. Methods: We have collected hematologic, biochemical, and coagulation data on 71 α1,3‐galactosyltransferase gene‐knockout (GTKO) pigs, 18 GTKO pigs additionally transgenic for human CD46 (GTKO.hCD46), four GTKO.hCD46 pigs additionally transgenic for human CD55 (GTKO.hCD46.hCD55), and two GTKO.hCD46 pigs additionally transgenic for human thrombomodulin (GTKO.hCD46.hTBM). Results: We report these data and compare them with similar data from wild‐type pigs and the three major NHP species commonly used in biomedical research (baboons, cynomolgus, and rhesus monkeys) and humans, largely from previously published reports. Conclusions: Genetic modification of the pig (e.g., deletion of the Gal antigen and/or the addition of a human transgene) (i) does not result in abnormalities in hematologic, biochemical, or coagulation parameters that might impact animal welfare, (ii) seems not to alter metabolic function of vital organs, although this needs to be confirmed after their xenotransplantation, and (iii) possibly (though, by no means certainly) modifies the hematologic, biochemical, and coagulation parameters closer to human values. This study may provide a good reference for those working with genetically engineered pigs in xenotransplantation research and eventually in clinical xenotransplantation.     

Insulin secretion and glucose metabolism in alpha 1,3‐galactosyltransferase knock‐out pigs compared to wild‐type pigs

Casu A, Echeverri GJ, Bottino R, van der Windt DJ, He J, Ekser B, Ball S, Ayares D, Cooper DKC. Insulin secretion and glucose metabolism in alpha 1,3‐galactosyltransferase knock‐out pigs compared to wild‐type pigs. Xenotransplantation 2010; 17: 131–139. © 2010 John Wiley & Sons A/S. Abstract: Background: Xenotransplantation of porcine islets could be a valuable alternative to the shortage of human islets for transplantation. To overcome the immunological obstacle of antibody‐mediated rejection, pigs homozygous for α1,3‐galactosyltransferase gene knock‐out (GT‐KO) have been produced. The effect of this mutation on glucose metabolism is unknown. Methods: Glucose, insulin, C‐peptide and glucagon levels were studied in eight adult pigs (four wild‐type [WT] and four GT‐KO) during intravenous glucose tolerance test (IVGTT), arginine stimulation test (AST), and insulin tolerance test (ITT). Morphological analysis of the pancreata was also performed. The in vitro insulin response to a high glucose concentration and theophylline were studied in a dynamic perfusion system with isolated islets. Results: Basal and stimulated blood glucose levels were similar in WT and GT‐KO pigs. Basal insulin, C‐peptide and glucagon were higher in GT‐KO pigs. C‐peptide and insulin responses to arginine and glucose were also higher in GT‐KO animals. The reduction in blood glucose during ITT and IVGTT was similar in WT and GT‐KO pigs. The extent of staining for insulin and glucagon in the pancreata were similar. The basal insulin secretion of isolated islets was higher in GT‐KO pigs, while stimulation indexes for glucose and theophylline were similar to WT. Conclusions: GT‐KO pigs demonstrated differences in glucose metabolism compared to WT pigs, the cause for which remains uncertain. It is unlikely that these differences would in any way affect the outcome of GT‐KO porcine islet xenotransplantation.     

Attitude toward xenotransplantation of patients prior and after human organ transplantation

Stadlbauer V, Stiegler P, Müller S, Schweiger M, Sereingg M, Tscheliessnigg KH, Freidl W. Attitude toward xenotransplantation of patients prior and after human organ transplantation.
Clin Transplant 2011: 25: 495–503. © 2010 John Wiley & Sons A/S. Abstract: Xenotransplantation is a potential strategy to overcome the shortage of human donor organs. As this technique has a major medical and psychological impact on patients and their family and friends, the attitude of patients currently waiting for organ transplantation is important. Therefore, we conducted a survey on the attitude toward xenotransplantation of patients on the waiting list and already transplanted patients. Patients received detailed information before being asked to fill in the questionnaire. We found that 65% would accept xenotransplantation, irrespective of gender, education level or if the patients were on the waiting list or already transplanted. The most common concern was transmission of diseases or genetic material, followed by psychological concerns and ethical issues. More patients had a positive attitude toward accepting cell or tissue transplantation when compared to whole organs. Pig pancreas islet cell transplantation is generally well accepted, patients with diabetes mellitus show even higher acceptance rates than patients without diabetes. In conclusion, xenotransplantation seems to be well accepted in patients who are potential future candidates for organ transplantation. Informing patients about the current status of research tended to decrease acceptance rates slightly.     

First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes—Executive summary

The International Xenotransplantation Association has updated its original “Consensus Statement on Conditions for Undertaking Clinical Trials of Porcine Islet Products in Type 1 Diabetes,” which was published in Xenotransplantation in 2009. This update is timely and important in light of scientific progress and changes in the regulatory framework pertinent to islet xenotransplantation. Except for the chapter on “informed consent,” which has remained relevant in its 2009 version, all other chapters included in the initial consensus statement have been revised for inclusion in this update. These chapters will not provide complete revisions of the original chapters; rather, they restate the key points made in 2009, emphasize new and under‐appreciated topics not fully addressed in 2009, suggest relevant revisions, and communicate opinions that complement the consensus opinion. Chapter 1 provides an update on national regulatory frameworks addressing xenotransplantation. Chapter 2 a, previously Chapter 2, suggests several important revisions regarding the generation of suitable source pigs from the perspective of the prevention of xenozoonoses. The newly added Chapter 2b discusses conditions for the use of genetically modified source pigs in clinical islet xenotransplantation. Chapter 3 reviews porcine islet product manufacturing and release testing. Chapter 4 revisits the critically important topic of preclinical efficacy and safety data required to justify a clinical trial. The main achievements in the field of transmission of all porcine microorganisms, the rationale for more proportionate recipient monitoring, and response plans are reviewed in Chapter 5. Patient selection criteria and circumstances where trials of islet xenotransplantation would be both medically and ethically justified are examined in Chapter 6 in the context of recent advances in available and emerging alternative therapies for serious and potentially life‐threatening complications of diabetes. It is hoped that this first update of the International Xenotransplantation Association porcine islet transplant consensus statement will assist the islet xenotransplant scientific community, sponsors, regulators, and other stakeholders actively involved in the clinical translation of islet xenotransplantation.     

Safety of xenotransplantation: screening the donor pig and the recipient

Introduction: Xenotransplantation using pig cells and tissues may be associated with the transmission of porcine microorganisms including bacteria, parasites, fungi and viruses to the human recipient and may result in zoonones. Porcine endogenous retroviruses (PERVs) represent a special risk since PERV‐A and PERV‐B are present in the genome of all pigs and infect human cells. PERV‐C is not present in all pigs and does not infect human cells. However, recombinants between PERV‐A and PERV‐C have been observed in normal pigs characterised by higher replication rates compared with PERV‐A, and they are also able to infect human cells (1). Methods: In the past years numerous assays based on the PCR technology have been developed to screen for the prevalence and expression of PERV and other porcine microorganisms in the donor pig (2). Whereas most microorganisms may be eliminated by designated pathogen‐free breeding, PERVs cannot be removed this way. In addition, assays have been developed to analyse the recipient for the transmission of PERV and other microorganisms, either using PCR methods or immunological assays to detect an antibody production as a result of infection (3). Results: Using these assays, no transmission of PERV as well as of other porcine microorganisms has been observed in first preclinical and clinical xenotransplantations or animal infection experiments. This was especially true for the first clinical transplantation of pig islet cells approved by the New Zealand government (4). Until now there is no susceptible animal model to study PERV transmission and transplantations of porcine cells or organs to non‐human primates as they are associated with limitations concerning the safety aspect, which do not allow transmitting the negative findings to humans (5). Different experimental approaches are under development to reduce the probability of PERV transmission, e.g. the generation of transgenic pigs expressing PERV‐specific siRNA inhibiting PERV expression by RNA interference (6), genotypic selection of pigs with a low prevalence and expression of PERV and neutralising antibodies against the envelope proteins inhibiting PERV infection (7). Conclusion: Investigations of the last years resulted in highly sensitive and specific methods to study PERV and other microorganisms in donor pigs and human recipients of xenotransplants. These methods showed absence of PERV transmission in all investigated cases, both in more than 200 human xenotransplant recipients, mostly recipients of cellular xenotransplants, as well as in non‐human primates and small animals. New technologies under development may further decrease the probability of transmission. References: 1. Denner J. Recombinant porcine endogenous retroviruses (PERV‐A/C): A new risk for xenotransplantation? Arch Virol 2008; 153: 1421–1426. 2. Kaulitz D, Mihica D, Dorna J, Costa MR, Petersen B, Niemann H, TÖnjes RR, Denner J. Development of sensitive methods for detection of porcine endogenous retrovirus‐C (PERV‐C) in the genome of pigs J Virol Methods 2011; 175(1): 60–65. 3. Denner, J. Infectious risk in xenotransplantation – what post‐transplant screening for the human recipient? Xenotransplantation 2011; 18(3): 151–157. 4. Wynyard S, Garkavenko O, Nathu D, Denner J, Elliott R. Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand, submitted. 5. Mattiuzzo G, Takeuchi Y. Suboptimal porcine endogenous retrovirus infection in non‐human primate cells: implication for preclinical xenotransplantation. PLoS One 2010; 5(10): e13203. 6. Semaan M, Kaulitz D, Petersen B, Niemann H, Denner J. Long‐term effects of PERV‐specific RNA interference in transgenic pigs. Xenotransplantation 2012; 19(2): 112–21. 7. Kaulitz D, Fiebig U, Eschricht M, Wurzbacher C, Kurth R, Denner J. Generation of neutralising antibodies against porcine endogenous retroviruses (PERVs). Virology 2011; 411(1): 78–86.     

Public opinion surveys about xenotransplantation

BACKGROUND: Xenotransplantation may eventually provide a solution to the worldwide shortage of human organs for transplantation. Xenotransplantation is surrounded by profound ethical issues, both for the potential recipients and for the society as a whole. Concurrent with increased scientific interest, there has been an increasing number of quantitative public opinion surveys conducted about xenotransplantation in the last decade. The aim of the present study was to elucidate these surveys, and to assess some factors that may affect the outcome of them. MATERIALS AND METHODS: Surveys were identified by web and literature searches using key words in Medline and ISI Web of Knowledge. Reference lists of identified surveys were checked. Data was obtained from Inter-University Consortium for Political and Social Research (ICPSR) and directly from authors whose data were presented in another way than percentages. In total, the present material covered surveys from 35 sources, including 23 countries. RESULTS AND DISCUSSION: Results showed that almost half of the respondents accept xenotransplantation, whereas the remaining half did either not accept or did not have/state an opinion. Over time, the proportions of acceptance seemed unchanged. The proportion of those who did not accept decreased and the remaining proportion increased. This pattern was evident in Europe and the US, but not in Japan. Gender and education were found to be associated with opinions to xenotransplantation. The influence of religion was not as straightforward. This may partly depend on how religiosity was measured in the polls. Wording of items influenced levels of acceptance. If a xenotransplant was the 'only choice' proportions of acceptance increased, and if a 'risk for zoonotic diseases' was stated proportions of acceptance decreased. When wording of survey items was somewhat comparable, there were often, but not always, minor differences in proportions of acceptance between surveys from different sources. Trends in opinions are best measured by the use of the same items. It is however difficult to phrase items that will not be affected by external events.     

Islet isolation and purification from inbred Wuzhishan miniature pigs

Jiang X, Qian T, Linn T, Cao L, Xiang G, Wang Y, Peng H, Xue P, Zhang L, Chen D, Yang X. Islet isolation and purification from inbred Wuzhishan miniature pigs. Xenotransplantation 2012; 19: 159–165. © 2012 John Wiley & Sons A/S. Abstract: Background: To investigate the applicability of inbred Wuzhishan (WZS) miniature pigs for porcine islet isolation and purification. Methods: Islet isolation and purification was conducted on adult (1‐yr‐old), male inbred WZS miniature pigs and age‐ and sex‐matched market pigs obtained from a local slaughterhouse (control group). Pancreata were excised, and islet isolation was carried out by static digestion and discontinuous gradient centrifugation. Viability of the purified islets was tested by radioimmunochemistry assay to measure glucose‐induced insulin release in culture and transplantation in an in vivo study. Results: The anatomical structure of the WZS miniature pig pancreas was more similar to the human pancreas than that of the market pig. Islet yield of the WZS miniature pigs’ pancreata was significantly higher than that of the market pigs (6078 ± 1105 vs. 2500 ± 625 islet equivalents [IEQ]/g). In vitro study demonstrated that the islets isolated from WZS miniature pigs were viable, as they efficiently responded to glucose challenge. In vivo study showed that the islets from both groups could cure the diabetic rat with the survival varied from 3 to 5 days (median, 4.3 days) and 2–4 days (median, 3.6 days) in experimental group and control group, respectively. Conclusion: Wuzhishan miniature pig pancreas may be a feasible source of islets for xenotransplantation.     

Pig‐to‐human xenotransplantation summit in Changsha,China

Cooper DKC, Schuurman H‐J. Pig‐to‐human xenotransplantation summit in Changsha, China. Xenotransplantation 2012; 19: 327–328. © 2012 John Wiley & Sons A/S. Abstract: On August 18 to 19, 2012, a meeting “Pig‐to‐Human Xenotransplantation Summit” was held in Changsha, Hunan, China, by Dr. Wei Wang. This summit highlighted important progress in the field in China. We here present a report from this meeting.     

Xenotransplantation: back to the future?

The field of xenotransplantation has fluctuated between great optimism and doubts over the last 50 years. The initial clinical attempts were extremely ambitious but faced technical and ethical issues that prompted the research community to go back to preclinical studies. Important players left the field due to perceived xenozoonotic risks and the lack of progress in pig‐to‐nonhuman‐primate transplant models. Initial apparently unsurmountable issues appear now to be possible to overcome due to progress of genetic engineering, allowing the generation of multiple‐xenoantigen knockout pigs that express human transgenes and the genomewide inactivation of porcine endogenous retroviruses. These important steps forward were made possible by new genome editing technologies, such as CRISPR/Cas9, allowing researchers to precisely remove or insert genes anywhere in the genome. An additional emerging perspective is the possibility of growing humanized organs in pigs using blastocyst complementation. This article summarizes the current advances in xenotransplantation research in nonhuman primates, and it describes the newly developed genome editing technology tools and interspecific organ generation.     

First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes – Chapter 1: update on national regulatory frameworks pertinent to clinical islet xenotransplantation

Islet xenotransplantation represents an attractive solution to overcome the shortage of human islets for use in type 1 diabetes. The wide‐scale application of clinical islet xenotransplantation, however, requires that such a procedure takes place in a specifically and tightly regulated environment. With a view to promoting the safe application of clinical islet xenotransplantation, a few years ago the International Xenotransplantation Association (IXA) published a Consensus Statement that outlined the key ethical and regulatory requirements to be satisfied before the initiation of xenotransplantation studies in diabetic patients. This earlier IXA Statement also documented a disparate regulatory landscape among different geographical areas. This situation clearly fell short of the 2004 World Health Assembly Resolution WHA57.18 that urged Member States “to cooperate in the formulation of recommendations and guidelines to harmonize global practices” to ensure the highest ethical and regulatory standards on a global scale. In this new IXA report, IXA members who are active in xenotransplantation research in their respective geographic areas herewith briefly describe changes in the regulatory frameworks that have taken place in the intervening period in the various geographic areas or countries. The key reassuring take‐home message of the present report is that many countries have embraced the encouragement of the WHO to harmonize the procedures in a more global scale. Indeed, important regulatory changes have taken place or are in progress in several geographic areas that include Europe, Korea, Japan, and China. Such significant regulatory changes encompass the most diverse facets of the clinical application of xenotransplantation and comprise ethical aspects, source animals and product specifications, study supervision, sample archiving, patient follow‐up and even insurance coverage in some legislations. All these measures are expected to provide a better care and protection of recipients of xenotransplants but also a higher safety profile to xenotransplantation procedures with an ultimate net gain in terms of international public health.     

Xenotransplantation from the ethical viewpoint. An outline]

The duty to save and to preserve lives on one hand, and the scarcity of human donor organs on the other hand call for a search for new organ sources, including xenogenic ones. Xenotransplantation, however, is not only in need of medical research, but also of ethical analysis. The latter is not to be considered a substitute for moral intuition, but rather a foundation of it by way of a critical evaluation of the ethical principles and reasons involved. This basically demands an analysis of the legitimacy of the aims and of the acceptability of the means for xenotransplantation. It includes safeguarding informed consent; risk assessment and the protection of not only the recipient, but also others; the question of limitation of personal rights; allocation problems; and last but not least animal protection. The aim is to clarify the ethical status of xenotransplantation in general and the question of a moratorium regarding clinical trials due to unsolved problems of infectivity and immunosuppression in particular by way of an integrative approach to both scientific developments and ethical analysis.     

Hepatocyte xenotransplantation for treating liver disease

Bonavita AG, Quaresma K, Cotta‐de‐Almeida V, Alves Pinto M, Magalhães Saraiva R, Anastácio Alves L. Hepatocyte xenotransplantation for treating liver disease. Xenotransplantation 2010; 17: 181–187. © 2010 John Wiley & Sons A/S. Abstract: The treatment of acute and chronic liver failure is still a challenge despite modern therapeutic innovations. While liver transplantation can restore liver function and improve patient survival, donor shortages limit this treatment to a small number of patients. Cellular xenotransplantation has emerged as an alternative for treating liver failure. Xenohepatocytes could be readily available in sufficient quantities to treat patients in critical condition and thereby reduce the donor shortage. The use of isolated encapsulated or non‐encapsulated cells can reduce the immunorejection response. Several studies using animal models of acute or chronic liver failure have demonstrated improved survival and recovery of liver function after xenotransplantation of adult hepatocytes. Porcine liver cells are a potential source of xenohepatocytes due to similarities with human physiology and the great number of hepatocytes that can be obtained. The recent development of less immunogenic transgenic pigs, new immunosuppressive drugs, and cellular encapsulation systems represents important advances in the field of cellular xenotransplantation. In this study, we review the work carried out in animal models that deals with the advantages and limitations of hepatocyte xenotransplantation, and we propose new studies needed in this field.