Organs For Transplantation Research Articles

Criminology characteristics of a person who commits smuggling transplant organs and other human anatomical materials

Criminology characteristics of a person who commits smuggling transplant organs and other human anatomical materials

Organ Utilization From Donors Following Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review of Graft and Recipient Outcome.

The global shortage of solid organs for transplantation is exacerbated by high demand, resulting in organ deficits and steadily growing waiting lists. Diverse strategies have been established to address this issue and enhance organ availability, including the use of organs from individuals who have undergone extracorporeal cardiopulmonary resuscitation (eCPR). The main aim of this work was to examine the outcomes for both graft and recipients of solid organ transplantations sourced from donors who underwent eCPR. We performed a systematic literature review using a combination of the terms related to extracorporeal life support and organ donation. Using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, PubMed and Scopus databases were searched up to February 2024. From 1764 considered publications, 13 studies comprising 130 donors and 322 organ donations were finally analyzed. On average, included patients were 36 y old, and the extracorporeal life support was used for 4 d. Kidneys were the most often transplanted organs (68%; 220/322), followed by liver (22%; 72/322) and heart (5%; 15/322); with a very good short-term graft survival rate (95% for kidneys, 92% for lungs, 88% for liver, and 73% for heart). Four studies with 230 grafts reported functional outcomes at the 1-y follow-up, with graft losses reported for 4 hearts (36%), 8 livers (17%), and 7 kidneys (4%). Following eCPR, organs can be successfully used with very high graft and recipient survival. In terms of meeting demand, the use of organs from patients after eCPR might be a suitable method for expanding the organ donation pool.

632 Hepatitis C Positive Organ Donation and Direct Acting Antivirals in Pancreas Transplantation: A Systematic Review

Abstract Background Pancreas transplantation (PT) provides diabetic cure for patients with complicated diabetes mellitus. However, there is a paucity of suitable donor organs to fulfil requirements resulting in deaths on the waiting list. Organs from otherwise suitable hepatitis C virus positive (HCV+) donors alongside direct-acting antiviral agents (DAAs) have been used in kidney and liver transplants in small trials. We aimed to review this strategy in PT. Method A literature search was conducted on OVID MedLINE, PubMed and EMBASE to evaluate evidence on the use of HCV+ organ donors for PT in HCV- recipients alongside DAA therapy. Results Database analysis produced 5 articles (4 single centre retrospective, 1 case report). This included a total of 65 patients, 15 of which received PT. Two studies examined multiple organ transplants whilst 3 evaluated PT alone. Three studies employed prophylactic perioperative therapy, while 2 examined treatment post-transplantation. 100% of patients achieved a sustained virological response (SVR) at 12 weeks across all 5 studies. There were no episodes of acute rejection or complications directly associated with DAA therapy or HCV infection. HCV transmission occurred in only 1 of 15 patients, which was successfully treated. Pancreatic graft function and outcome after 7-12 months was good. Conclusions The use of DAA therapy is safe and effective for HCV+ donors to HCV- transplant in early reported studies. This approach could facilitate the successful utilisation of HCV+ organs for transplantation thereby minimising impact on supply and demand disparities. Pancreas transplantation specific studies are required to further analyse outcomes.

Regional variation in donation after circulatory death heart allograft utilization

ObjectiveRandomized data support transplantation of hearts from donors after circulatory death. This may lead to a sizeable increase in the donor pool. Regional variations in donors after circulatory death heart use were examined to help elucidate barriers to donor pool expansion. MethodsThe United Network for Organ Sharing deceased donor dataset was queried for adult (age ≥ 18 years) donors after circulatory death donors of at least 1 organ between January 2020 and December 2023. Donors were stratified by the extent their respective cardiac allografts progressed through the donation process. United Network for Organ Sharing region-level use rates and annual trends were assessed. ResultsOf 17,239 adult donors after circulatory death donors who donated at least 1 organ for transplant during the study period, 1196 (9.4%) were heart donors. Regional donors after circulatory death heart donor pursuit rates ranged from 97% to 100%, consent attainment rates from 94% to 99%, and heart recovery rates from 5% to 10%. The transplantation rate of recovered organs ranged from 90% to 97%. Multivariable logistic regression demonstrated United Network for Organ Sharing region to be independently associated with donors after circulatory death heart use after controlling for baseline differences in donor risk. ConclusionsTransplantation of donors after circulatory death heart allografts has increased in the United States since 2020, but the overall number of hearts procured and transplanted from donors after circulatory death donors remains low. The operational barriers to transplantation of donors after circulatory death hearts require further investigation. Further, significant regional variation exists regarding rates of progression of donors after circulatory death hearts through the donation process. Sharing of successful practices among Organ Procurement Organizations and transplant centers will facilitate maximal use of this new donor pool.

Infectious Diseases and Clinical Xenotransplantation.

Xenotransplantation, transplantation into humans of vascularized organs or viable cells from nonhuman species, is a potential solution to shortages of transplantable human organs. Among challenges to application of clinical xenotransplantation are unknown risks of transmission of animal microbes to immunosuppressed recipients or the community. Experience in allotransplantation and in preclinical models suggests that viral infections are the greatest concern. Worldwide, the distribution of swine pathogens is heterogeneous and cannot be fully controlled by international agricultural regulations. It is possible to screen source animals for potential human pathogens before procuring organs in a manner not possible within the time available for surveillance testing in allotransplantation. Infection control measures require microbiological assays for surveillance of source animals and xenograft recipients and research into zoonotic potential of porcine organisms. Available data suggest that infectious risks of xenotransplantation are manageable and that clinical trials can advance with appropriate protocols for microbiological monitoring of source animals and recipients.

Public attitudes to xenotransplantation: A national survey in the United States

Xenotransplantation (XTx) presents a potential clinical alternative to the shortage of human organs for transplantation. Before clinical trials occur in the United States, public assessments are crucial to understand potential barriers to acceptance. The purpose of this study was to explore barriers and identify characteristics associated with attitudes toward XTx. A survey assessing demographic characteristics and attitudes toward XTx was distributed to a nationally representative sample of adults aged ≥18 years in the United States. Regression analysis was employed to identify characteristics associated with attitudes toward XTx. Between May 25 and June 14, 2023, 5008 respondents completed the survey. Importantly, half of the respondents expressed low or no knowledge of either transplantation or XTx. Approximately 40% expressed discomfort with receiving a pig organ for themselves or a loved one. Despite a lack of xenotransplant outcome data, 36% were open to experimental XTx if they needed a transplant. However, 57% rated lack of current evidence of success or fear of complications as top concerns. Regression models consistently associated being younger, female, not needing an organ, or being a member of a racial minority group with lower acceptance. This survey is the largest to date exploring public attitudes toward XTx. Despite overall acceptance, concerns persist. Increasing public acceptance is key as the field advances.

In Defense of Normothermic Regional Perfusion.

Normothermic regional perfusion (NRP) is a relatively new approach to procuring organs for transplantation. After circulatory death is declared, perfusion is restored to either the thoracoabdominal organs (in TA-NRP) or abdominal organs alone (in A-NRP) using extracorporeal membrane oxygenation. Simultaneously, surgeons clamp the cerebral arteries, causing a fatal brain injury. Critics claim that clamping the arteries is the proximate cause of death in violation of the dead donor rule and that the procedure is therefore unethical. We disagree. This account does not consider the myriad other factors that contribute to the death of the donor, including the presence of a fatal medical condition, the decision to withdraw life support, and the physician's actions in withdrawing life support and administering medication that may hasten death. Instead, we claim that physicians play a causative role in many of the events that lead to a patient's death and that these actions are often ethically and legally justified. We advance an "all things considered" view according to which TA-NRP may be considered ethically acceptable insofar as it avoids suffering and respects the wishes of the patient to improve the lives of others through organ donation. We conclude with a series of critical questions related to the practice of NRP and call for the development of national consensus on this issue in the United States.

Factors Responsible for Nonselection of Donors in Living Related Kidney Transplantation.

Living donor kidney transplant is the preferred method of renal transplant in Pakistan as deceased donor transplant has not yet been estab-lished. However, many patients who are dialysis-dependent, particularly younger patients, lack suitable living related donors. We aimed to determine factors contributing to nonselection of donors for living related renal transplant in Pakistan. For this cross-sectional study, we included patients seen at the Sindh Institute of Urology & Transplantation Karachi, Pakistan) from March to November 2019. Potential donors were adult family members who accompanied patients with end-stage kidney disease to the clinic. Demographic and clinical information were recorded on predesigned proforma. After workup and baseline investigations had been completed, potential living related donors were selected. Factors leading to nonselection of donors were noted for those who did not qualify for donation. We used SPSS version 20 for analysis. During the study period, 253 potential donors (151 males, 102 females) with mean age of 35.68 ± 6.14 years were found to be ineligible for kidney donation. ABO incompatibility was the most common factor leading to nonselection (n = 101; 39.92%), followed by diabetes mellitus (n = 71; 28.06%), hypertension (n= 50; 19.76%), renal disease (n = 15; 5.92%), liver disease (n = 8; 3.16%), crossmatch positive (n = 5; 1.97%), and ischemic heart disease (n = 3; 1.18%). No differences were shown between potential male and female donors regarding factors leading to nonselection; diabetes was significantly more prevalent among those <40 years of age (P = .025). ABO incompatibility, diabetes mellitus, and hypertension were the most common factors leading to nonselection of potential donors in living related kidney transplant. More efforts are needed to expand the donor pool by considering second- or third-degree relatives to tackle the scarcity of organs for transplantation.

Liver bioprinting within a novel support medium with functionalized spheroids, hepatic vein structures, and enhanced post-transplantation vascularization

Cell-laden bioprinting is a promising biofabrication strategy for regenerating bioactive transplants to address organ donor shortages. However, there has been little success in reproducing transplantable artificial organs with multiple distinctive cell types and physiologically relevant architecture. In this study, an omnidirectional printing embedded network (OPEN) is presented as a support medium for embedded 3D printing. The medium is state-of-the-art due to its one-step preparation, fast removal, and versatile ink compatibility. To test the feasibility of OPEN, exceptional primary mouse hepatocytes (PMHs) and endothelial cell line-C166, were used to print hepatospheroid-encapsulated-artificial livers (HEALs) with vein structures following predesigned anatomy-based printing paths in OPEN. PMHs self-organized into hepatocyte spheroids within the ink matrix, whereas the entire cross-linked structure remained intact for a minimum of ten days of cultivation. Cultivated HEALs maintained mature hepatic functions and marker gene expression at a higher level than conventional 2D and 3D conditions in vitro. HEALs with C166-laden vein structures promoted endogenous neovascularization in vivo compared with hepatospheroid-only liver prints within two weeks of transplantation. Collectively, the proposed platform enables the manufacture of bioactive tissues or organs resembling anatomical architecture, and has broad implications for liver function replacement in clinical applications.

The journey of decellularized vessel: from laboratory to operating room.

Over the past few decades, there has been a remarkable advancement in the field of transplantation. But the shortage of donors is still an urgent problem that requires immediate attention. As with xenotransplantation, bioengineered organs are promising solutions to the current shortage situation. And decellularization is a unique technology in organ-bioengineering. However, at present, there is no unified decellularization method for different tissues, and there is no gold-standard for evaluating decellularization efficiency. Meanwhile, recellularization, re-endothelialization and modification are needed to form transplantable organs. With this mind, we can start with decellularization and re-endothelialization or modification of small blood vessels, which would serve to address the shortage of small-diameter vessels while simultaneously gathering the requisite data and inspiration for further recellularization of the whole organ-scale vascular network. In this review, we collect the related experiments of decellularization and post-decellularization approaches of small vessels in recent years. Subsequently, we summarize the experience in relation to the decellularization and post-decellularization combinations, and put forward obstacle we face and possible solutions.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant.

With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed. Exclusion criteria included patients who were not solid organ donors, patients who were not declared brain dead (donation after circulatory death), and patients who did not receive steroids in their hospital course. Levothyroxine and steroid administration, the number of organs donated, the types of organs donated, and demographic information were recorded. Univariate analyses were performed with P < 0.05 considered to be statistically significant. A total of 88 patients met inclusion criteria, 69 (78%) of whom received levothyroxine and steroids (ST/LT group) vs 19 (22%) receiving steroids without levothyroxine (ST group). No differences were observed between the groups for gender, race, pertinent injury factors, age, or other hormone therapies used (P > 0.05). In the ST/LT group, 68.1% (n = 47) donated a high yield (3-5) of organ types per donor compared to 42.1% (n = 8) in the ST group (P = 0.038). There was no difference in the total number of organ types donated between the groups (P = 0.068). This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population. Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria. This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.

Immunoprotection Strategies in β-Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.

Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency primarily due to autoimmune destruction of pancreatic β-cells. The prevailing treatment for T1DM involves daily subcutaneous insulin injections, but a substantial proportion of patients face challenges such as severe hypoglycemic episodes and poorly controlled hyperglycemia. For T1DM patients, a more effective therapeutic option involves the replacement of β-cells through allogeneic transplantation of either the entire pancreas or isolated pancreatic islets. Unfortunately, the scarcity of transplantable human organs has led to a growing list of patients waiting for an islet transplant. One potential alternative is xenotransplantation of porcine pancreatic islets. However, due to inter-species molecular incompatibilities, porcine tissues trigger a robust immune response in humans, leading to xenograft rejection. Several promising strategies aim to overcome this challenge and enhance the long-term survival and functionality of xenogeneic islet grafts. These strategies include the use of islets derived from genetically modified pigs, immunoisolation of islets by encapsulation in biocompatible materials, and the creation of an immunomodulatory microenvironment by co-transplanting islets with accessory cells or utilizing immunomodulatory biomaterials. This review concentrates on delineating the primary obstacles in islet xenotransplantation and elucidates the fundamental principles and recent breakthroughs aimed at addressing these challenges.

Pig organs in humans: a forum on xenotransplantation

ABSTRACT What if one of your organs, say, the kidney, the heart or the liver, deteriorates completely, and you are not lucky enough to have a human organ for transplantation? Do you want to receive an organ from a pig? That is not a joke, but a subject some physicians and researchers are working on—a field of research known as ‘xenotransplantation’.In 2022, David Bennett, a 57-year-old patient with terminal heart disease, received a pig heart and survived for 2 months after the surgery. Another recipient, Lawrence Faucette, survived for 40 days after similar surgery in 2023. Then, in 2024, Rick Slayman, the world's first recipient of a pig kidney, passed away 2 months after the surgery. Rick was able to get out of the hospital during these 2 months and the transplant team said there is no indication that his sudden passing was the result of failure of the pig kidney graft. Rather, it was related to his heart disease. In China, a liver xenotransplantation from pig to a brain-dead patient was reported in 2024 and the transplanted liver survived in the human body for as long as 10 days.On April 2024, National Science Review organized a panel discussion on xenotransplantation, which was chaired by Prof. Liangxue Lai and involved six other experts in the field. The panelists had in-depth discussions on xenotransplantation, covering its history and the (i) gene editing of the donor pigs, (ii) immunosuppressive regimens required by the recipients, (iii) challenges in preclinical and clinical research, (iv) relevant ethical issues and (v) prospects for the future of xenotransplantation. Gang Chen Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China David K.C. Cooper Massachusetts General Hospital, Harvard Medical School, Boston, USA Yifan Dai School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China Dengke Pan ClonOrgan Biotechnology Company, Neijiang, China Lin Wang Xijing Hospital, Air Force Medical University, Xi'an, China Xuan Zhang Xijing Hospital, Air Force Medical University, Xi'an, China Liangxue Lai (Chair) Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China

Heart immunoengineering by lentiviral vector-mediated genetic modification during normothermic ex vivo perfusion.

Heart transplantation is associated with major hurdles, including the limited number of available organs for transplantation, the risk of rejection due to genetic discrepancies, and the burden of immunosuppression. In this study, we demonstrated the feasibility of permanent genetic engineering of the heart during ex vivo perfusion. Lentiviral vectors encoding for short hairpin RNAs targeting beta2-microglobulin (shβ2m) and class II transactivator (shCIITA) were delivered to the graft during two hours of normothermic EVHP. Highly efficient genetic engineering was indicated by stable reporter gene expression in endothelial cells and cardiomyocytes. Remarkably, swine leucocyte antigen (SLA) class I and SLA class II expression levels were decreased by 66% and 76%, respectively, in the vascular endothelium. Evaluation of lactate, troponin T, and LDH levels in the perfusate and histological analysis showed no additional cell injury or tissue damage caused by lentiviral vectors. Moreover, cytokine secretion profiles (IL-6, IL-8, and TNF-α) of non-transduced and lentiviral vector-transduced hearts were comparable. This study demonstrated the ex vivo generation of genetically engineered hearts without compromising tissue integrity. Downregulation of SLA expression may contribute to reduce the immunogenicity of the heart and support graft survival after allogeneic or xenogeneic transplantation.

Vertical Takeoff and Landing for Distribution of Parcels to Hospitals: A Case Study about Industry 5.0 Application in Israel’s Healthcare Arena

To gain a sustained competitive advantage, organizations such as UPS, Fedex, Amazon, etc., began to seek for industry 5.0 innovative autonomous delivery options for the last mile. Autonomous unmanned aerial vehicles are a promising alternative for the logistics industry. The fact that drones are propelled by green renewable energy source fits the companies’ need to become sustainable, replacing their fuel truck fleets, especially for traveling to remote rural locations to deliver small packages, but a major obstacle is the necessity for charging stations which is well documented in the literature. Therefore, the current research embarks on devising a novel yet practical piece of technology adopting the simplicity approach of direct flights to destinations. The analysis showcases the application for a network of warehouses and hospitals in Israel while controlling costs. Given the products in the case study are medical, direct flight has the potential to save lives when every moment counts. Hydrogen cell technology allows long-range flying without refueling, and it is both vibration-free which is essential for sensitive medical equipment and environmentally friendly in terms of air pollution and silence in urban areas. Importantly, hydrogen cells are lighter, with higher energy density than batteries, which makes them ideal for drone usage to reduce weight, maintain a longer life, and enable faster charging, all of which minimize downtime. Also, hydrogen sourcing is low-cost and unlimited compared to lithium-ion material which needs to be mined. The case study investigates an Israeli entrepreneurial company, Gadfin, which builds a vertical takeoff-and-landing-type of drone with folded wings that enable higher speed for the delivery of refrigerated medical cargo, blood, organs for transplant, and more to hospitals in partnership with the Israeli medical logistic conglomerate, SAREL. An analysis of shipping optimization (concerning the number and type of drone) is conducted using a mixed-integer linear programming technique based on various types of constraints such as traveling distance, parcel weight, the amount of flight controllers and daily number of flights allowed in order to not overcrowd the airspace. Importantly, the discussion assesses the ecosystem’s variety of risks and commensurate safety mechanisms for advancing a newly shaped landscape of drones in an Israeli tight airspace to establish a network of national routes for drone traffic. The conclusion of this research cautions limitations to overcome as the utilization of drones expand and offers future research avenues.

Introduction of Hybrid Additive Manufacturing for Producing Multi-Material Artificial Organs for Education and In Vitro Testing

The evolution of 3D printing has ushered in accessibility and cost-effectiveness, spanning various industries including biomedical engineering, education, and microfluidics. In biomedical engineering, it encompasses bioprinting tissues, producing prosthetics, porous metal orthopedic implants, and facilitating educational models. Hybrid Additive Manufacturing approaches and, more specifically, the integration of Fused Deposition Modeling (FDM) with bio-inkjet printing offers the advantages of improved accuracy, structural support, and controlled geometry, yet challenges persist in cell survival, interaction, and nutrient delivery within printed structures. The goal of this study was to develop and present a low-cost way to produce physical phantoms of human organs that could be used for research and training, bridging the gap between the use of highly detailed computational phantoms and real-life clinical applications. To this purpose, this study utilized anonymized clinical Computed Tomography (CT) data to create a liver physical model using the Creality Ender-3 printer. Polylactic Acid (PLA), Polyvinyl Alcohol (PVA), and light-bodied silicone (Polysiloxane) materials were employed for printing the liver including its veins and arteries. In brief, PLA was used to create a mold of a liver to be filled with biocompatible light-bodied silicone. Molds of the veins and arteries were printed using PVA and then inserted in the liver model to create empty channel. In addition, the PVA was then washed out by the final product using warm water. Despite minor imperfections due to the printer’s limitations, the final product imitates the computational model accurately enough. Precision adjustments in the design phase compensated for this variation. The proposed novel low-cost 3D printing methodology successfully produced an anatomically accurate liver physical model, presenting promising applications in medical education, research, and surgical planning. Notably, its implications extend to medical training, personalized medicine, and organ transplantation. The technology’s potential includes injection training for medical professionals, personalized anthropomorphic phantoms for radiation therapy, and the future prospect of creating functional living organs for organ transplantation, albeit requiring significant interdisciplinary collaboration and financial investment. This technique, while showcasing immense potential in biomedical applications, requires further advancements and interdisciplinary cooperation for its optimal utilization in revolutionizing medical science and benefiting patient healthcare.

Organ Donation by the Imminently Dead: Addressing the Organ Shortage and the Dead Donor Rule.

The dead donor rule (DDR) has facilitated the saving of hundreds of thousands of lives. Recent advances in heart donation, however, have exposed how DDR has limited donation of all organs. We propose advancing the moment in the dying process at which death can be determined to increase substantially the supply of organs for transplantation. We justify this approach by identifying certain flaws in the Uniform Determination of Death Act and proposing a modification of that law that permits earlier procurement of healthier organs in greater numbers.

Platform for Organ Donation and Transplantation Using Blockchain

The critical shortage of organs for transplantation necessitates exploring innovative solutions to improve the matching and allocation process.

Organ Donation Management using Blockchain

This research paper focuses mainly on the scarcity of organs for transplantation underscores the urgent need for innovative solutions to enhance the matching and allocation process.

Effect of the Organ Donation Quality System on Donation Activity of Warsaw Hospitals.

BACKGROUND Like many other countries, Poland faces a shortage of transplantable organs despite implementing strategies to develop donation programs. Increasing the effectiveness of deceased organ donation programs requires the implementation of protocols and quality standards for the entire process. The aim of this study was to assess the organ donation potential in Warsaw hospitals (with and without implemented donation procedures) in the years 2017-2018, before the COVID-19 pandemic affected donation activity. The obtained results were compared with quality indicators established in the ODEQUS project and the European Commission project "Improving Knowledge and Practices in Organ Donation" (DOPKI). MATERIAL AND METHODS Retrospective analysis was performed of hospitalization and death causes (including deaths in the brain death mechanism) in the hospitals and intensive care units in 2017-2018. We divided 15 Warsaw hospitals into 2 groups: those with implemented quality programs for organ donation (n=4) and those without such programs (n=11). RESULTS Hospitals with procedures obtained significantly higher values than hospitals without procedures, but were lower than the values in DOPKI and ODEQUS. The success rate of the organ donation process after brain death recognition was comparable in all groups. The conversion rate to actual donors was 73% in hospitals with procedures compared to 68% in hospitals without procedures, significantly higher than in the 42% reported in the DOPKI project. CONCLUSIONS Low numbers of brain death declarations in Warsaw hospitals result from low recognition of deaths in the brain death mechanism. Implementing procedures at each hospital level will enable identification of critical points and comparison of solution outcomes.