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Cardiac xenotransplantation (cXT) has emerged as a solution to heart donor scarcity, prompting an exploration of its scientific, ethical, and regulatory facets. The review begins with genetic modifications enhancing pig hearts for human transplantation, navigating through immunological challenges, rejection mechanisms, and immune responses. Key areas include preclinical milestones, complement cascade roles, and genetic engineering to address hyperacute rejection. Physiological counterbalance systems, like human thrombomodulin and endothelial protein C receptor upregulation in porcine xenografts, highlight efforts for graft survival enhancement. Evaluating pig and baboon donors and challenges with non-human primates illuminates complexities in donor species selection. Ethical considerations, encompassing animal rights, welfare, and zoonotic disease risks, are critically examined in the cXT context. The review delves into immune control mechanisms with aggressive immunosuppression and clustered regularly interspaced palindromic repeats associated protein 9 (CRISPR/Cas9) technology, elucidating hyperacute rejection, complement activation, and antibody-mediated rejection intricacies. CRISPR/Cas9’s role in creating pig endothelial cells expressing human inhibitor molecules is explored for rejection mitigation. Ethical and regulatory aspects emphasize the role of committees and international guidelines. A forward-looking perspective envisions precision medical genetics, artificial intelligence, and individualized heart cultivation within pigs as transformative elements in cXT’s future is also explored. This comprehensive analysis offers insights for researchers, clinicians, and policymakers, addressing the current state, and future prospects of cXT.
Cardiac xenotransplantation (cXT) has emerged as a solution to heart donor scarcity, prompting an exploration of its scientific, ethical, and regulatory facets. The review begins with genetic modifications enhancing pig hearts for human transplantation, navigating through immunological challenges, rejection mechanisms, and immune responses. Key areas include preclinical milestones, complement cascade roles, and genetic engineering to address hyperacute rejection. Physiological counterbalance systems, like human thrombomodulin and endothelial protein C receptor upregulation in porcine xenografts, highlight efforts for graft survival enhancement. Evaluating pig and baboon donors and challenges with non-human primates illuminates complexities in donor species selection. Ethical considerations, encompassing animal rights, welfare, and zoonotic disease risks, are critically examined in the cXT context. The review delves into immune control mechanisms with aggressive immunosuppression and clustered regularly interspaced palindromic repeats associated protein 9 (CRISPR/Cas9) technology, elucidating hyperacute rejection, complement activation, and antibody-mediated rejection intricacies. CRISPR/Cas9’s role in creating pig endothelial cells expressing human inhibitor molecules is explored for rejection mitigation. Ethical and regulatory aspects emphasize the role of committees and international guidelines. A forward-looking perspective envisions precision medical genetics, artificial intelligence, and individualized heart cultivation within pigs as transformative elements in cXT’s future is also explored. This comprehensive analysis offers insights for researchers, clinicians, and policymakers, addressing the current state, and future prospects of cXT.
Liver transplantation represents a pivotal intervention in the management of end-stage liver disease, offering a lifeline to countless patients. Despite significant strides in surgical techniques and organ procurement, ethical dilemmas and debates continue to underscore this life-saving procedure. Navigating the ethical terrain surrounding this complex procedure is hence paramount. Dissecting the nuances of ethical principles of justice, autonomy and beneficence that underpin transplant protocols worldwide, we explore the modern challenges that plaques the world of liver transplantation. We investigate the ethical dimensions of organ transplantation, focusing on allocation, emerging technologies, and decision-making processes. PubMed, Scopus, Web of Science, Embase and Central were searched from database inception to February 29, 2024 using the following keywords: “liver transplant”, “transplantation”, “liver donation”, “liver recipient”, “organ donation” and “ethics”. Information from relevant articles surrounding ethical discussions in the realm of liver transplantation, especially with regards to organ recipients and allocation, organ donation, transplant tourism, new age technologies and developments, were extracted. From the definition of death to the long term follow up of organ recipients, liver transplantation has many ethical quandaries. With new transplant techniques, societal acceptance and perceptions also play a pivotal role. Cultural, religious and regional factors including but not limited to beliefs, wealth and accessibility are extremely influential in public attitudes towards donation, xenotransplantation, stem cell research, and adopting artificial intelligence. Understanding and addressing these perspectives whilst upholding bioethical principles is essential to ensure just distribution and fair allocation of resources. Robust regulatory oversight for ethical sourcing of organs, ensuring good patient selection and transplant techniques, and high-quality long-term surveillance to mitigate risks is essential. Efforts to promote equitable access to transplantation as well as prioritizing patients with true needs are essential to address disparities. In conclusion, liver transplantation is often the beacon of hope for individuals suffering from end-stage liver disease and improves quality of life. The ethics related to transplantation are complex and multifaceted, considering not just the donor and the recipient, but also the society as a whole.
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