Organs For Transplantation Research Articles

Quantitative Abdominal Arterial Calcification Correlates with Kidney Transplant Waitlist Mortality

Introduction: The scarcity of available organs for kidney transplantation has resulted in a substantial waiting time for patients with end-stage kidney disease. This prolonged wait contributes to an increased risk of cardiovascular mortality. Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, and it is common among candidates for kidney transplant. The aim of this study was to correlate abdominal arterial calcification (AAC) score value with mortality on the waitlist. Methods: We modified the coronary calcium score and used it to quantitate the AAC. We conducted a retrospective clinical study of all adult patients who were listed for kidney transplant, between 2005 and 2015, and had abdominal computed tomography scan. Patients were divided into two groups: those who died on the waiting list group and those who survived on the waiting list group. Results: Each 1,000 increase in the AAC score value of the sum score of the abdominal aorta, bilateral common iliac, bilateral external iliac, and bilateral internal iliac was associated with increased risk of death (HR 1.034, 95% CI: 1.013, 1.055) (p = 0.001). This association remained significant even after adjusting for various patient characteristics, including age, tobacco use, diabetes, coronary artery disease, and dialysis status. Conclusion: The study highlights the potential value of the AAC score as a noninvasive imaging biomarker for kidney transplant waitlist patients. Incorporating the AAC scoring system into routine imaging reports could facilitate improved risk assessment and personalized care for kidney transplant candidates.

Introduction of ex vivo perfusion of extended-criteria donor hearts in a single center in Asia.

The shortage of organs for heart transplantation has created a need to explore the use of extended-criteria organs. We report the preliminary use of normothermic TransMedics Organ Care System-an ex vivo approach to preserve extended-criteria brain-dead donor hearts. This System maintains a normal temperature, provides continuous perfusion and oxygenation, reduces ischemic time, and enables additional viability assessment options. In a retrospective single-centre study conducted from April 2020 to March 2023, four extended criteria brain-dead donor hearts were perfused and monitored using the Organ Care System. Suitability for transplantation was assessed based on stable or decreasing lactate levels, along with appropriate perfusion parameters. The Organ Care for use of the Organ Care System were coronary artery disease, left ventricular hypertrophy, high-dose inotrope use in the donor, a downtime exceeding 20min, and a left ventricular ejection fraction of 40-50%. Three out of the four donor hearts were transplanted, while one was discarded due to rising lactate concentration. The three recipients had a higher surgical risk profile for heart transplant. All showed normal cardiac function and no primary graft dysfunction postoperatively. At 2-3years post-transplant, all recipients have a ventricular function of > 60%, with only one showing evidence of mild rejection. The Organ Care System enables the successful transplantation of marginal donor organs in high-risk recipients, showcasing the feasibility of recruiting donors with extended criteria. This technique is safe and promising, expanding the donor pool and addressing the organ shortage in heart transplantation in Hong Kong.

Mesendodermal cells fail to contribute to heart formation following blastocyst injection.

Blastocyst complementation offers an opportunity for generating transplantable whole organs from donor sources. Pluripotent stem cells (PSCs) have traditionally served as the primary donor cells due to their ability to differentiate into any type of body cell. However, the use of PSCs raises ethical concerns, particularly regarding their uncontrollable differentiation potential to undesired cell lineages such as brain and germline cells. To address this issue, various strategies have been explored, including the use of genetically modified PSCs with restricted lineage potential or lineage-specified progenitor cells as donors. In this study, we tested whether nascent mesendodermal cells (MECs), which appear during early gastrulation, can be used as donor cells. To do this, we induced Bry-GFP+ MECs from mouse embryonic stem cells (ESCs) and introduced them into the blastocyst. While donor ESCs gave rise to various regions of embryos, including the heart, Bry-GFP+ MECs failed to contribute to the host embryos. This finding suggests that MECs, despite being specified from PSCs within a few days, lack the capacity to assimilate into the developing embryo.

Optimizing Resuscitation of the Donation after Circulatory Death Heart by Mitochondrial Protection in a Female Porcine Model.

Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death [DCD]). Using a translational porcine model of DCD, this study developed and evaluated a protocol based on cardioprotection by multidrug postconditioning to optimize resuscitation of DCD hearts during ex situ heart perfusion (ESHP). Hearts of female pigs (45.0 ± 4.5 kg) were procured following a clinically identical DCD protocol, consisting of the termination of ventilator support and confirmation of circulatory arrest, followed by a 15-min standoff period. DCD hearts were randomly allocated to ESHP (38.4°C) in the absence (untreated, N = 5) or presence (treated, N = 5) of a postconditioning treatment added to the perfusate, consisting of Intralipid (1%), sevoflurane (2% v/v), and remifentanil (3 nM). All hearts were perfused with blood and Krebs-Henseleit solution (1:1) for 60 min in Langendorff mode and for an additional 300 min in working mode for a total perfusion time of 6 h. Oxidative capacity and detailed left ventricular mechanical function under an increasing workload (left atrial pressure, 6 to 12 mmHg) were assessed hourly. Left ventricular tissue was snap-frozen at the end of ESHP and used for molecular analyses. Left ventricular inotropy (LVdP/dtmax) did not decline over time in treated DCD hearts and was significantly higher at the end of the protocol as compared with untreated DCD hearts (ΔLVdP/dtmax = 440 mmHg/s; P = 0.009). Treated DCD hearts exhibited persistently higher left ventricular stroke work index during the 6-h period of ESHP, whereas untreated DCD hearts displayed a significant decline (change in left ventricular stroke work index = -3.10 ml · mmHg/g; P(time within untreated group) < 0.001). Treated DCD hearts displayed higher metabolic activity as measured by oxygen consumption (ΔO2 = 3.11 ml O2 · min-1 · 100 g-1; P = 0.004) and released lower amounts of cell-free mitochondrial DNA into the perfusate, a marker of potential graft dysfunction. Treated hearts also used fatty acids from Intralipid as an energy source, whereas untreated DCD hearts showed glyceroneogenesis with triglyceride accumulation and depletion of tricarboxylic acid cycle intermediates; reduced mitochondrial complex I, II, and III activities with accumulation of mitochondrial NADH, and signs of ultrastructural damage. A translationally relevant protective ESHP protocol consisting of treatment with Intralipid, sevoflurane, and remifentanil markedly accelerated functional recovery and improved viability of DCD hearts.

Transcriptional Profiling Underscores the Role of Preprocurement Allograft Metabolism and Innate Immune Status on Outcomes in Human Liver Transplantation.

The adverse effects of ischemia-reperfusion injury (IRI) remain a principal barrier to a successful outcome after lifesaving orthotopic liver transplantation (OLT). Gene expression during different phases of IRI is dynamic and modified by individual exposures, making it attractive for identifying potential therapeutic targets for improving the number of suitable organs for transplantation and patient outcomes. However, data remain limited on the functional landscape of gene expression during liver graft IRI, spanning procurement to reperfusion and recovery. Therefore, we sought to characterize transcriptomic profiles of IRI during multiple phases in human OLT. We conducted clinical data analyses, histologic evaluation, and RNA sequencing of 17 consecutive human primary OLT. We performed liver allograft biopsies at 4 time points: baseline (B, before donor cross-clamp), at the end of cold ischemia (CI), during early reperfusion (ER, after revascularization), and during late reperfusion (LR). Data were generated and then recipients grouped by post-OLT outcomes categories: immediate allograft function (IAF; n = 11) versus early allograft dysfunction (EAD; n = 6) groups. We observed that CI (vs B) modified a transcriptomic landscape enriched for a metabolic and immune process. Expression levels of hallmark inflammatory response genes were higher transitioning from CI to ER and decreased from ER to LR. IAF group predominantly showed higher bile and fatty acid metabolism activity during LR compared with EAD group, while EAD group maintained more immunomodulatory activities. Throughout all time points, EAD specimens exhibited decreased metabolic activity in both bile and fatty acid pathways. We report transcriptomic profiles of human liver allograft IRI from prepreservation in the donor to posttransplantation in the recipient. Immunomodulatory and metabolic landscapes across ER and LR phases were different between IAF and EAD allografts. Our study also highlights marker genes for these biological processes that we plan to explore as novel therapeutic targets or surrogate markers for severe allograft injury in clinical OLT.

Post-human Bodies in Atwood’s Oryx and Crake

This paper analyses the human bodies as a site of both aesthetics as well as politics in post-human turn in the novel Oryx and Crake by Margaret Atwood. Questions related to what is a body, who controls it, and what relation does it have to morality at techno-science culture share a negotiation between machine and morality. After the advent of popular culture, the concept of body as cogent and self-bounded entity is blurry one as the discourse of ‘what is a beautiful body’ reflects a growing concern with different approaches of body aesthetics. As seen the novel, Oryx and Crake by Margaret Atwood, we see Crakers— the genetically modified humans as an outcome of Crake’s aesthetics and politics. Jimmy’s father’s involvement in Pigoon Projects designed with the intention of providing human organs for transplantation and Crake’s involvement in creating Crakers—whom Crake had programmed to die at 30 open a new avenue for discussion regarding human identity. Such dimension of body aesthetics is precarious leading to ethical question as progress in science does not only enhance body, it also poses a threat to humanity in entirety. This research is qualitative and interpretive in nature. So, as a researcher, I have brought theoretical insights related to trans-humanism and post-humanism developed by Fukuyama, Braidotti. In the paper, I conclude that though new version of body aesthetics poses a threat to the world itself, it helps to understand how humans have co-evolved with other companion species. Thus, it contributes on the discussion of literary engagement and literary understanding of post humanism.

Dysregulation of Immune Tolerance to Autologous iPSCs and Their Differentiated Derivatives.

Induced pluripotent stem cells (iPSCs), capable of differentiating into any cell type, are a promising tool for solving the problem of donor organ shortage. In addition, reprogramming technology makes it possible to obtain a personalized, i.e., patient-specific, cell product transplantation of which should not cause problems related to histocompatibility of the transplanted tissues and organs. At the same time, inconsistent information about the main advantage of autologous iPSC-derivatives - lack of immunogenicity - still casts doubt on the possibility of using such cells beyond immunosuppressive therapy protocols. This review is devoted to immunogenic properties of the syngeneic and autologous iPSCs and their derivatives, as well as to the reasons for dysregulation of their immune tolerance.

PERSPECTIVE: The cold chain delivery of organs for transplantation: from research laboratories and individual enthusiasts to pan-global networks in 50 years

It is some 50 years since the first published reports appeared of ex vivo preservation of organs for transplantation. Over the intervening decades, organ preservation strategies have become one essential component of world-wide clinical transplant services. In the formative years, translational research in organ hypothermic preservation was grappling with the questions about whether static or dynamic storage was preferable, and the practical implications of those choices. Those studies were also informing the newly expanding clinical transplant services. During the middle years, both preservation modalities were practiced by individual group choices. By the 2000???s, the shift in donor demographics demanded a re-evaluation of organ preservation strategies, and now a new era of research and development is promoting adoption of new technologies. In this review we outline many important academic studies which have contributed to this successful history, and give profile to the increasing innovative approaches which are being evaluated for the future.

Knowledge, Attitude, and Practice of Organ Donation Among the Population of Al-Majma'ah Region, Saudi Arabia.

Organ donation plays a pivotal role in addressing the global demand for transplantable organs and saving lives. The success of organ transplantation relies not only on medical advancements but also on the willingness of communities to participate in organ donation programs. In Saudi Arabia, specifically within the Al-Majma'ah region, understanding the dynamics of knowledge, attitudes, and practices related to organ donation is crucial for promoting a sustainable and ethical organ donation system. A cross-sectional, retrospective study was utilized in this research, employing data from a sample of 564 participants from the general population of the Al-Majma'ah region, Saudi Arabia. The participants completed a self-administered questionnaire and ensured anonymity. About 545 (96.6%) respondents were familiar with the concept of organ donation, and 455 (80.7%) participants recognized the necessity for the blood groups of the donor and recipient to match before the transplant process. About 412 (73.0%) participants agreed with the practice of organ donation with 326 (57.8%) expressing support for the practice. About 417 (73.9%) participants reported that their religion permits or endorses organ donation/transplantation. A total of 151 individuals (26.8%) had a low knowledge level, with total scores below 50%(6 or lower). In contrast, 280 people (4.7%) demonstrated a moderate level of knowledge (scoring between 50% and 75%) (7 to 9). Additionally, 133 individuals (23.5%) showcased a high level of knowledge, with scores exceeding 75%(10 or higher). The study established a statistically significant association between age, marital status with p-values < 0.05 (0.001*), and the knowledge score towardorgan donation. However, genderand monthly household income were not significantly associated with knowledge score towardorgan transplant with p-values (p-value > 0.05). The research findings indicated a moderate level of knowledge and a positive attitude toward organ donation among the general population of the Al-Majma'ah region in Saudi Arabia. Age and marital status were found to be significantly associated with the knowledge score towardorgan donation. The study noted the desire and willingness to save lives through organ donation by the residents of the Al-Majma'ah region in Saudi Arabia.

Membrane supported liquid-liquid oxygenation for use in extracorporeal life support – Proof of principle

Chronic respiratory diseases are the third most frequent cause of death worldwide. However, the limited availability of transplantable organs led to an increased research effort in artificial lung systems. Current artificial lung systems use hollow fibre membrane-based oxygenators. Historic oxygenators using a direct liquid-gas or liquid-liquid interface outperformed todays hollow-fibre technology in terms of gas-transfer. However, these approaches were no longer pursued due to risk of embolization by gas or liquid droplet formation in the blood stream. The herein presented approach of a membrane-supported liquid-liquid oxygenator combines todays hollow-fibre technology with historic liquid-liquid approaches to achieve a stable interface without the risk of embolization but with the advantages of a higher gas-transfer and a decreasing foreign membrane surface of the oxygenator. Perfluoro-n-hexane was chosen as a hemocompatible carrier fluid for the presented liquid-liquid approach. In the proof-of-principle oxygenator, O2 and CO2 gas-transfers were measured to be 1.83 mmolO2 and 1.34 mmolCO2, respectively. No Perfluoro-n-hexane droplets were detected in the blood after the experiment. This study demonstrates the proof of principle of a new membrane-supported liquid-liquid oxygenator.

Activation of farnesoid X receptor enhances the efficacy of normothermic machine perfusion in ameliorating liver ischemia-reperfusion injury

The shortage of transplant organs remains a severe global issue. Normothermic machine perfusion (NMP) has the potential to increase organ availability, yet its efficacy is hampered by the inflammatory response during machine perfusion. Mouse liver ischemia-reperfusion injury (IRI) models, discarded human liver models, and porcine marginal liver transplantation models were utilized to investigate whether farnesoid X receptor (FXR) activation could mitigate inflammation-induced liver damage. FXR expression levels before and after reperfusion were measured. Gene editing and coimmunoprecipitation techniques were employed to explore the regulatory mechanism of FXR in inflammation inhibition. The expression of FXR correlates with the extent of liver damage after reperfusion. Activation of FXR significantly suppressed the inflammatory response triggered by IRI, diminished the release of proinflammatory cytokines, and improved liver function recovery during NMP, assisting discarded human livers to reach transplant standards. Mechanistically, FXR disrupts the interaction between p65 and p300, thus inhibiting modulating the nuclear factor kappa-B signaling pathway, a key instigator of inflammation. Our research across multiple species confirms that activating FXR can optimize NMP by attenuating IRI-related liver damage, thereby improving the utilization of marginal livers for transplantation.

Bridging the Gap in Cryopreservation Mechanism: Unraveling the Interplay between Structure, Dynamics, and Thermodynamics in Cryoprotectant Aqueous Solutions.

Cryoprotectants play a crucial role in preserving biological material, ensuring their viability during storage and facilitating crucial applications such as the conservation of medical compounds, tissues, and organs for transplantation. However, the precise mechanism by which cryoprotectants modulate the thermodynamic properties of water to impede the formation and growth of ice crystals, thus preventing long-term damage, remains elusive. This is evident in the use of empirically optimized recipes for mixtures that typically contain DMSO, glycerol, and various sugar constituents. Here, we use terahertz calorimetry, Overhauser nuclear polarization, and molecular dynamics simulations to show that DMSO exhibits a robust structuring effect on water around its methyl groups, reaching a maximum at a DMSO mole fraction of XDMSO = 0.33. In contrast, glycerol exerts a smaller water-structuring effect, even at higher concentrations (Scheme 1). These results potentially suggest that the wrapped water around DMSO's methyl group, which can be evicted upon ligand binding, may render DMSO a more surface-active cryoprotectant than glycerol, while glycerol may participate more as a viscogen that acts on the entire sample. These findings shed light on the molecular intricacies of cryoprotectant solvation behavior and have potentially significant implications for optimizing cryopreservation protocols.

Optimal strategies for prevention of ischemia‑reperfusion injury in heart transplantation with prolonged cold ischemia time (review)

The shortage of organs for transplant remains a major challenge in transplantology. Transporting donor organs over long distances increases cold ischemia time, which is a risk factor for ischemia-reperfusion injury (IRI). In the face of critical shortages, the method and timing of organ preservation are crucial in increasing the donor pool. This paper examines the approaches, benefits, and drawbacks of organ preservation techniques used around the world.

Hypothermic oxygenated perfusion in liver transplantation from expanded criteria donors

Objective: to improve the outcomes of liver transplantation (LTx) from expanded criteria donors (ECDs) through hypothermic oxygenated machine perfusion (HOPE).Material and methods. The study included 63 cases of LTx from suboptimal brain-dead donors. Group I (control) consisted of 34 persons in which liver transplant was preserved only by static cold storage (SCS), while group II (main) comprised 29 cases where ex situ HOPE was used after static preservation. We evaluated the efficacy and safety of the latter in a comparative clinical study and by studying ultrastructural changes in the liver using electron microscopy.Results. No statistically significant differences between the groups in terms of baseline characteristics of donors, recipients and several perioperative parameters (p &gt; 0.05) were obtained. Peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the first week after transplantation were 1,052 (IQR: 712–1,842) U/L and 1,213 (IQR: 613–2,032) U/L in the HOPE group, and 1,943 (IQR: 1,294–5,214) U/L and 2,318 (IQR: 1,032–6,219) U/L in the SCS group (control). The levels were statistically significantly lower (p = 0.002 and p &lt; 0.001, respectively). Median comprehensive complication index (CCI) in the main and control groups was 0 (IQR: 0–22.6) and 27.6 (IQR: 0–100) respectively. The differences were statistically significant (p = 0.001). Similarly, statistically significant differences were noted in terms of recipient time in the intensive care unit (ICU) and overall length of hospital stay (p = 0.042 and p = 0.028) – they were less in the HOPE group. Electron microscopy evaluation of the morphology of liver grafts revealed that hepatocytes sustained less injury during HOPE.Conclusion. Ex situ HOPE is a safe and effective way of preserving liver transplants. Its use in LTx from expanded criteria donors can lessen the severity of ischemia-reperfusion injury (IRI) in the organ and enable additional assessment of the suitability of an organ for transplantation.

Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation.

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of xenotransplantation research. It begins by examining the mechanisms through which xenotransplantation activates both the classical and alternative complement pathways. It then assesses the current landscape of xenotransplantation from donor pigs, with a particular emphasis on the innovative strides made in genetically engineering pigs to evade complement system activation. These modifications are critical in mitigating the discordance between pig endogenous retroviruses and human immune molecules. Additionally, the review discusses pharmacological interventions designed to support transplantation. By exploring the intricate relationship between the complement system and xenotransplantation, this retrospective analysis not only underscores the scientific and clinical importance of this field but also sheds light on the potential pathways to overcoming one of the major barriers to the success of xenografts. As such, the insights offered here hold significant promise for advancing xenotransplantation from a research concept to a viable clinical reality.

Public Opinions on Removing Disincentives and Introducing Incentives for Organ Donation: Proposing a European Research Agenda.

The shortage of organs for transplantations is increasing in Europe as well as globally. Many initiatives to the organ shortage, such as opt-out systems for deceased donation and expanding living donation, have been insufficient to meet the rising demand for organs. In recurrent discussions on how to reduce organ shortage, financial incentives and removal of disincentives, have been proposed to stimulate living organ donation and increase the pool of available donor organs. It is important to understand not only the ethical acceptability of (dis)incentives for organ donation, but also its societal acceptance. In this review, we propose a research agenda to help guide future empirical studies on public preferences in Europe towards the removal of disincentives and introduction of incentives for organ donation. We first present a systematic literature review on public opinions concerning (financial) (dis)incentives for organ donation in European countries. Next, we describe the results of a randomized survey experiment conducted in the United States. This experiment is crucial because it suggests that societal support for incentivizing organ donation depends on the specific features and institutional design of the proposed incentive scheme. We conclude by proposing this experiment's framework as a blueprint for European research on this topic.

Organ Donation in Syria.

The first living donor kidney transplant in Syria was performed 44 years ago; by the end of 2022, 6265 renal transplants had been performed in Syria. Kidney, bone marrow, cornea, and stem cells are the only organs or tissues that can be transplanted in Syria. Although 3 heart transplants from deceased donors were performed in the late 1980s, cardiac transplant activities have since discontinued. In 2003, national Syrian legislation was enacted authorizing the use of organs from living unrelated and deceased donors. This important law was preceded by another big stride: the acceptance by the higher Islamic religious authorities in Syria in 2001 of the principle of procurement of organs from deceased donors, provided that consent is given by a first- or second-degree relative. After the law was enacted, kidney transplant rates increased from 7 per million population in 2002 to 17 per million population in 2007. Kidney transplants performed abroad for Syrian patients declined from 25% in 2002 to <2% in 2007. Rates plateaued through 2010, before the political crisis started in 2011. Forty-four years after the first successful kidney transplant in Syria, patients needing an organ transplant rely on living donors only. Moreover, 20 years after the law authorizing use of organs from deceased donors, a program is still not in place in Syria. The war, limited resources, and lack of public awareness about the importance of organ donation and transplant appear to be factors inhibiting initiation of a deceased donor program in Syria. A concerted and ongoing education campaign is needed to increase awareness of organ donation, change negative public attitudes, and gain societal acceptance. Every effort must be made to initiate a deceased donor program to lessen the burden on living donors and to enable national self-sufficiency in organs for transplant.

Evolution of the Concept of Death.

The definition of death remains unresolved. To define death, one has to define the characteristics of a living person and to confirm whether an individual with brain death fulfils any of these characteristics. Although the concept of irreversible cessation of brain function is clear, controversy remains on the treatment of individuals with brain death and beating hearts. An individual with brain death but a beating heart is not breathing on his own and is dependent on medications and machines to maintain respiration, heartbeat, and blood pressure. Muslim scholars remain divided over the issue of whether death also means irreversible cessation of brain function. Questions remain on when it is permissible to remove vital organs for organ transplant. Groups have advocated for uniformity in law and medical practice on the definition of brain death.

A First Experience of Distant Lung Preservation for Transplantation in the Russian Federation.

Lung transplant is an effective method of treating patients with end-stage respiratory diseases, but problems such as the imbalance between the number of donor organs and the number ofrecipients needing organs still play a leading role. From a transplant point of view, a multiorgan donor is considered of greatest efficiency, so that all organs that can potentially be used should be transplanted. The combination of the vast geographical territory of Russia, the shortage of actual donors, and the relatively small number of transplant centers has led to the need to transport donor lungs by air over long distances. There were already precedents in the world for remote preservation of donor organs for transplant. In this study, we have described the unique experience of remote evaluation of donor lungs with their subsequent air transportation and transplantation, which is the first such description in Russia to our knowledge. The donor lungs for lung transplant were brought from medical institutions of the Samara region to Moscow. During remote evaluation, all information was transmitted to the transplant center by providing access to the automated information system "Organ Donation," which was used at that time by the service and contained all information about a potential donor in real time. The 2 transplant candidates had end-stage cystic fibrosis and severe respiratory failure; both patients underwent organ implantation from donors located outside their regions. In conditions of shortages of donor organs, long-distance transportation is a reasonable, feasible, and safe procedure.

A Remarkable Journey of Porcine to Human Xenotransplantation

Xenotransplantation of pig hearts offers a potential solution to the scarcity of available human organs for transplantation. This abstract explores the challenges and risks associated with xenotransplantation, as well as the ongoing research and development efforts aimed at overcoming these obstacles. The primary hurdle in pig-to-human heart transplantation is immunological compatibility, as the human immune system perceives pig organs as foreign and mounts a rejection response. Genetic engineering techniques are being investigated to modify pig organs and enhance compatibility with the human immune system. In addition, the risk of cross-species disease transmission, known as xenozoonosis, poses another concern. Researchers are actively working to identify and address these risks to ensure the safety of xenotransplantation. Although xenotransplantation of pig hearts is still in the experimental stage and not widely performed in clinical settings, numerous preclinical studies and clinical trials are underway to evaluate the safety and efficacy of the procedure. This abstract emphasizes the importance of ongoing research and development in the field, highlighting the potential of xenotransplantation as a viable solution for the organ shortage crisis. Ultimately, further advancements are necessary before xenotransplantation of pig hearts can be established as a routine clinical procedure.