Cost and Scalability Analysis of Porcine Islet Isolation for Islet Transplantation: Comparison of Juvenile, Neonatal and Adult Pigs.

The limited availability of human islets has led to the examination of porcine islets as a source of clinically suitable tissue for transplantation in patients with diabetes mellitus. Islets from porcine donors are commonly used in both in vitro and in vivo experiments studying diabetes mellitus. However, there are significant differences in quality and quantity of islet yield depending on donor pig age, as well as substantial differences in the costs of pancreas procurement in adult versus neonatal and juvenile pigs. In this study, we compared the total cost per islet of juvenile pig pancreata with that of neonatal and adult pigs. Although adult porcine pancreata yield, on average, more than five times the amount of islets than do juvenile and neonatal pancreata, we found that the high price of adult pigs led to the cost per islet being more than twice that of juvenile and neonatal islets (US $0.09 vs $0.04 and $0.02, respectively). In addition, neonatal and juvenile islets are advantageous in their scalability and retention of viability after culture. Our findings indicate that isolating neonatal and juvenile porcine islets is more cost-effective and scalable than isolating adult porcine islets.

Genetically-engineered pigs as sources for clinical red blood cell transfusion: What pathobiological barriers need to be overcome?

An alternative to human red blood cells (RBCs) for clinical transfusion would be advantageous, particularly in situations of massive acute blood loss (where availability and compatibility are limited) or chronic hematologic diseases requiring frequent transfusions (resulting in alloimmunization). Ideally, any alternative must be neither immunogenic nor pathogenic, but readily available, inexpensive, and physiologically effective. Pig RBCs (pRBCs) provide a promising alternative due to their several similarities with human RBCs, and our increasing ability to genetically-modify pigs to reduce cellular immunogenicity. We briefly summarize the history of xenotransfusion, the progress that has been made in recent years, and the remaining barriers. These barriers include prevention of (i) human natural antibody binding to pRBCs, (ii) their phagocytosis by macrophages, and (iii) the T cell adaptive immune response (in the absence of exogenous immunosuppressive therapy). Although techniques of genetic engineering have advanced in recent years, novel methods to introduce human transgenes into pRBCs (which do not have nuclei) will need to be developed before clinical trials can be initiated.

Clinical implementation of islet transplantation: A current assessment.

Beta-cell replacement is the only physiologically relevant alternative to insulin injections in patients with type 1 diabetes (T1D). Pancreas and islet transplantation from deceased organ donors can provide a new beta-cell pool to produce insulin, help blood glucose management, and delay secondary diabetes complications. For children and adolescents with T1D, whole pancreas transplantation is not a viable option because of surgical complications, whereas islet transplantation, even if it is procedurally simpler, must still overcome the burden of immunosuppression to become a routine therapy for children in the future.

A health-economic analysis of porcine islet xenotransplantation.

BACKGROUND: Islet cell transplantation is a promising treatment for type 1 diabetes. To overcome the shortage of deceased human pancreas donors, porcine islet cell xenotransplantation is being developed as an alternative to allotransplantation. The objective of this study was to perform a cost-effectiveness analysis of porcine islet transplantation in comparison with standard insulin therapy. The patient population for this study was young adults, ages 20 to 40, for whom standard medical care is inadequate in controlling blood glucose levels (hypoglycemia unawareness). Since trial data were lacking, estimates used extrapolations from data found in the literature and ongoing trials in clinical allotransplantation. Cost estimates were based on the data available in the USA. METHODS: Markov modeling and Monte Carlo simulations using software specifically developed for health-economic evaluations were used. Outcomes data for ongoing clinical islet allotransplantation from the University of Minnesota were used, along with probabilities of complications from the Diabetes Control and Complications Trial. Quality-adjusted life years (QALYs) were the effectiveness measure. The upper limit of being cost-effective is $100,000 per QALY. Cost data from the literature were used and adjusted to 2007 US dollars using the medical care portion of the Consumer Price Index. RESULTS: In both Markov modeling and Monte Carlo simulations, porcine islet xenotransplantation was both more effective and less costly over the course of the 20-yr model. For standard insulin therapy, cumulative cost per patient was $661,000, while cumulative effectiveness was 9.4 QALYs, for a cost of $71,100 per QALY. Transplantation had a cumulative cost of $659 000 per patient, a cumulative effectiveness of 10.9 QALYs, and a cost per QALY of $60,700. Islet transplantation became cost-effective at 4 yr after transplantation, and was more cost-effective than standard insulin treatment at 14 yr. These findings are related to relative high costs in the transplantation arm of the evaluation during the first years while those in the insulin arm became higher later in follow-up. Throughout the follow-up period, effectiveness of transplantation was higher than that of insulin treatment. In sensitivity analysis, duplication or triplication of one-time initial costs such as costs of donor animal, islet manufacturing and transplantation had no effect on long-term outcome in terms of cost-saving or cost-effectiveness, but the outcome of transplantation in terms of diabetes complications in cases with partial graft function could affect cost-saving and cost-effectiveness conclusions. CONCLUSION: Despite limitations in the model and lack of trial data, and under the assumption that islet transplantation outcomes for young adult type 1 diabetes patients are not dependent on the source of islet cells, this health-economic evaluation suggests that porcine islet cell xenotransplantation may prove to be a cost-effective and possibly cost-saving procedure for type 1 diabetes compared to standard management.

Xenotransplantation: a bioethical evaluation.

Allograft shortage is a formidable obstacle in organ transplantation. Xenotransplantation, the interspecies transplantation of cells, tissues, and organs, or ex vivo interspecies exchange between cells, tissues, and organs is a frequently suggested alternative to this allograft shortage. As xenotransplantation steadily improves into a viable allotransplantation alternative, several bioethical considerations coalesce. Such considerations include the Helsinki declaration's guarantee of patients' rights to privacy; political red tape that may select for undermined socioeconomic groups as the first recipients of xenografts; industry incentives in xenotransplantation investments; conflicts of interest when a clinician supervises a patient as a research subject; the psychosocial impact of transplantation on the xenograft recipient, and the rights of animals. This review illuminates these issues through a conglomeration of expert opinion and relevant experimental studies.

Heterotransplantation of kidney: medical and legal issues.

Since 1905, various attempts were made to transplant kidney from rabbit, pig or goat. But the attempts failed due to strong immune reaction-response. Heterotransplantation or xenotransplantation is a process to transplant kidney between various species. Allotransplantation is costly and needs lifelong immunosuppression associated with high risk rate of infection and other complications. Moreover legal and social issues involved in the process should be taken into account. So xenotransplantation is definitely an improved process.

Recommendations of the National Heart, Lung, and Blood Institute Heart and Lung Xenotransplantation Working Group.

The National Heart, Lung, and Blood Institute (NHLBI) recently convened the Heart and Lung Xenotransplantation Working Group to identify hurdles to the clinical application of xenotransplantation, defined as the use of animal organs or tissue for transplantation, and to recommend possible solutions to these problems. The group consisted of experts in xenotransplantation from academia, industry, and federal agencies, and the discussions focused on those areas within the mission of the NHLBI. The areas covered included immunologic and physiological barriers to xenotransplantation, the limitations of the current animal models, the need for collaboration among groups, the high costs of studies using nonhuman primates and genetic engineering of pigs, and the unique problems of lung xenotransplantation. This report is a summary of those discussions.

Xenotrasplante ¿Alternativa de futuro? Aspectos jurídicos / Xenotransplantation. An alternative for the future? Legal aspects

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Attitudes of potential candidates for heart and heart-lung transplantation to xenotransplantation.

CONTEXT AND OBJECTIVES: Whether the fact that a transplanted organ is non-human would affect acceptance levels among potential recipients of heart and heart-lung xenografts has not been determined. Studies in renal patients have produced contradictory results. Furthermore, no previous studies have examined the attitudes toward xenotransplantation among the chief caregivers of potential transplant recipients. PARTICIPANTS AND MEASURES: Fifty-nine patients and 54 caregivers responded to a questionnaire that requested their views on xenotransplantation, the source and level of their knowledge about xenotransplantation, and the perceived costs and benefits of this intervention. Patients' and caregivers' attitudes to animal experimentation and killing animals for human benefit were also assessed by using a specifically designed attitude questionnaire. RESULTS: Fifty-six percent of patients and 48% of caregivers were unsure about xenotransplantation. Seventy-nine percent of patients and 85% of caregivers indicated that they had received little or no information about xenotransplantation, and what information they had received was from nonmedical sources. Availability of organs was the main perceived benefit (36% of patients and 40% of caregivers) and ethical and moral issues were the main perceived cost (20% of patients and 25% of caregivers). Overall patients and caregivers were in agreement with animal experimentation and killing animals for human benefit. CONCLUSIONS: Potential heart and heart-lung recipients and their caregivers have limited information about xenotransplantation and are currently unsure about the acceptability of this procedure. Although this uncertainty may be due to their lack of information about this intervention, it may also reflect concerns about the morality of breeding animals solely to provide organs for transplantation.

Milking the genome for profit.

Despite recent accomplishments, significant challenges remain before cloning can become a routine part of transgenic animal production.

Animal farm--the ethics and public policy of xenotransplantation.

In 1997, over four thousand people on organ waiting lists lost their lives. The current organ shortage has led to the need to find alternative sources of organs for transplantation. Advances in immunosuppressive therapies and genetics have made xenotransplantation, the transplantation of animal organs into humans, an increasingly viable technology. However, the promise of xenotransplantation is tempered by the unspecified amount of risk that zoonotic pathogens could mutate and infect humans with potentially deadly diseases.

Issues surrounding xenotransplantation.

Currently there is a shortage of cadaver organs that can be transplanted from one human being to another. In response to this shortage, scientists and medical researchers have developed techniques for transplanting animal organs into humans, a procedure known as xenotransplantation. This may address the shortage of organs for patients in need; however, it raises other concerns related to cross-species disease transmission, consent issues, ethical issues of sacrificing animals for their organs, psychological issues of receiving organs from an animal, religious concerns, and economic factors. These medical, ethical, and philosophical issues need to be thoroughly addressed before xenotransplantation becomes a reality.