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Korean Journal of Transplantation Dec 2023Due to a critical organ shortage, pig organs are being explored for use in transplantation. Differences between species, particularly in cell surface glycans, can... (Review)
Review
Due to a critical organ shortage, pig organs are being explored for use in transplantation. Differences between species, particularly in cell surface glycans, can trigger elevated immune responses in xenotransplantation. To mitigate the risk of hyperacute rejection, genetically modified pigs have been developed that lack certain glycans and express human complement inhibitors. Nevertheless, organs from these pigs may still provoke stronger inflammatory and innate immune reactions than allotransplants. Dysregulation of coagulation and persistent inflammation remain obstacles in the transplantation of pig organs into primates. Regulatory macrophages (Mregs), known for their anti-inflammatory properties, could offer a potential solution. Mregs secrete interleukin 10 and transforming growth factor beta, thereby suppressing immune responses and promoting the development of regulatory T cells. These Mregs are typically induced via the stimulation of monocytes or macrophages with macrophage colony-stimulating factor and interferon gamma, and they conspicuously express the stable marker dehydrogenase/reductase 9. Consequently, understanding the precise mechanisms governing Mreg generation, stability, and immunomodulation could pave the way for the therapeutic use of Mregs generated . This approach has the potential to reduce the required dosages and durations of anti-inflammatory and immunosuppressive medications in preclinical and clinical settings.
PubMed: 38115165
DOI: 10.4285/kjt.23.0055 -
Clinical Transplantation Apr 2020Islam is the second most practiced religion globally, and the number of Muslims in Western countries has been increasing due to recent trends in migration. Studies have... (Review)
Review
Islam is the second most practiced religion globally, and the number of Muslims in Western countries has been increasing due to recent trends in migration. Studies have shown that Muslims in the Western world have more negative attitudes toward organ donation and transplantation compared with individuals from other religious backgrounds. Multiple barriers have been postulated that may prevent Muslims from exploring organ donation or transplantation. We conducted a literature review with the goal of summarizing the opinions of major Sunni and Shia scholars and Islamic bodies about organ donation and transplantation, including their opinions and rulings on the neurological determination of death to inform healthcare professionals, community members, and leaders. We also identified factors and attitudes that may prevent members of the Muslim community from achieving equitable access to transplantation or from consenting to donate organs during life or after death. Key factors or concerns identified included: lack of information regarding organ donation, mistrust of the healthcare system, family opinions, sacredness of the body, lack of clear understanding of religious rulings, and opinions of religious leaders. Studies have suggested that partnering with religious leaders to address these concerns may help foster positive attitudes toward organ donation and transplantation.
Topics: Humans; Islam; Organ Transplantation; Tissue Donors; Tissue and Organ Procurement
PubMed: 32068915
DOI: 10.1111/ctr.13832 -
Journal of Hepatology Oct 2022The COVID-19 pandemic has significantly changed organ donation and transplantation worldwide. Since the beginning of the pandemic, the uncertainty regarding the... (Review)
Review
The COVID-19 pandemic has significantly changed organ donation and transplantation worldwide. Since the beginning of the pandemic, the uncertainty regarding the potential route of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created tremendous pressures on transplantation communities, and international organisations have advised against using organs from deceased donors who have tested positive for SARS-CoV-2. The possibility of SARS-CoV-2 transmission through organ donation has only been reported for lung transplantation; hence, based on current experience, transplantation of non-lung organs from donors with active SARS-CoV-2 infection has been considered possible and safe, at least over short-term follow-up. As the evolving outbreak of SARS-CoV-2 continues, alongside the presence of vaccines and new treatment options, clinicians should consider transplanting organs from deceased donors with active SARS-CoV-2 infection to recipients with limited opportunities for transplantation and those with specific natural or vaccine-induced immunity. This article proffers an expert opinion on the use of organs from deceased donors with resolved or active SARS-CoV-2 infection in the absence of more definitive data and standardised acceptance patterns.
Topics: COVID-19; Humans; Organ Transplantation; Pandemics; SARS-CoV-2; Tissue Donors; Tissue and Organ Procurement
PubMed: 35798131
DOI: 10.1016/j.jhep.2022.06.021 -
Chemical Reviews Oct 2020The field of tissue engineering has advanced over the past decade, but the largest impact on human health should be achieved with the transition of engineered solid... (Review)
Review
The field of tissue engineering has advanced over the past decade, but the largest impact on human health should be achieved with the transition of engineered solid organs to the clinic. The number of patients suffering from solid organ disease continues to increase, with over 100 000 patients on the U.S. national waitlist and approximately 730 000 deaths in the United States resulting from end-stage organ disease annually. While flat, tubular, and hollow nontubular engineered organs have already been implanted in patients, in vitro formation of a fully functional solid organ at a translatable scale has not yet been achieved. Thus, one major goal is to bioengineer complex, solid organs for transplantation, composed of patient-specific cells. Among the myriad of approaches attempted to engineer solid organs, 3D bioprinting offers unmatched potential. This review highlights the structural complexity which must be engineered at nano-, micro-, and mesostructural scales to enable organ function. We showcase key advances in bioprinting solid organs with complex vascular networks and functioning microstructures, advances in biomaterials science that have enabled this progress, the regulatory hurdles the field has yet to overcome, and cutting edge technologies that bring us closer to the promise of engineered solid organs.
Topics: Bioprinting; Humans; Printing, Three-Dimensional; Tissue Engineering
PubMed: 32885956
DOI: 10.1021/acs.chemrev.0c00145 -
Gastroenterology & Hepatology Feb 2022Hepatitis C virus (HCV) infection is a common indication for liver transplantation. If the patient's HCV is untreated prior to liver transplant, infection of the...
Hepatitis C virus (HCV) infection is a common indication for liver transplantation. If the patient's HCV is untreated prior to liver transplant, infection of the allograft is nearly universal and can lead to graft failure. The demand for deceased-donor organ transplantation continues to surpass the available supply of donor organs. Waitlist mortality remains an important concern, and several strategies have been enacted to increase organ supply, such as using high-risk donors, including those who are HCV positive. The development of safe and highly effective HCV therapy with direct-acting antiviral agents has revolutionized the management of liver transplant candidates and transplantrecipients. Moreover, thenewer antiviral therapieshave paved the road for use of HCV-viremic organs, effectively expanding the donor pool and changing the landscape of solid organ transplantation. This article reviews the data on HCV treatment prior to and after organ transplantation.
PubMed: 35505819
DOI: No ID Found -
Frontiers in Immunology 2021The complexity of transplant medicine pushes the boundaries of innate, human reasoning. From networks of immune modulators to dynamic pharmacokinetics to variable... (Review)
Review
The complexity of transplant medicine pushes the boundaries of innate, human reasoning. From networks of immune modulators to dynamic pharmacokinetics to variable postoperative graft survival to equitable allocation of scarce organs, machine learning promises to inform clinical decision making by deciphering prodigious amounts of available data. This paper reviews current research describing how algorithms have the potential to augment clinical practice in solid organ transplantation. We provide a general introduction to different machine learning techniques, describing their strengths, limitations, and barriers to clinical implementation. We summarize emerging evidence that recent advances that allow machine learning algorithms to predict acute post-surgical and long-term outcomes, classify biopsy and radiographic data, augment pharmacologic decision making, and accurately represent the complexity of host immune response. Yet, many of these applications exist in pre-clinical form only, supported primarily by evidence of single-center, retrospective studies. Prospective investigation of these technologies has the potential to unlock the potential of machine learning to augment solid organ transplantation clinical care and health care delivery systems.
Topics: Clinical Decision-Making; Data Mining; Decision Support Techniques; Diagnosis, Computer-Assisted; Graft Survival; Humans; Machine Learning; Organ Transplantation; Postoperative Complications; Predictive Value of Tests; Risk Assessment; Risk Factors; Therapy, Computer-Assisted; Time Factors; Treatment Outcome
PubMed: 34603324
DOI: 10.3389/fimmu.2021.739728 -
American Journal of Transplantation :... Sep 2022The COVID-19 pandemic has influenced organ transplantation decision making. Opinions regarding the utilization of coronavirus disease-2019 (COVID-19) donors are mixed....
The COVID-19 pandemic has influenced organ transplantation decision making. Opinions regarding the utilization of coronavirus disease-2019 (COVID-19) donors are mixed. We hypothesize that COVID-19 infection of deceased solid organ transplant donors does not affect recipient survival. All deceased solid organ transplant donors with COVID-19 testing results from March 15, 2020 to September 30, 2021 were identified in the OPTN database. Donors were matched to recipients and stratified by the COVID-19 test result. Outcomes were assessed between groups. COVID-19 test results were available for 17 694 donors; 150 were positive. A total of 269 organs were transplanted from these donors, including 187 kidneys, 57 livers, 18 hearts, 5 kidney-pancreases, and 2 lungs. The median time from COVID-19 testing to organ recovery was 4 days for positive and 3 days for negative donors. Of these, there were 8 graft failures (3.0%) and 5 deaths (1.9%). Survival of patients receiving grafts from COVID-19-positive donors is equivalent to those receiving grafts from COVID-19-negative donors (30-day patient survival = 99.2% COVID-19 positive; 98.6% COVID-19 negative). Solid organ transplantation using deceased donors with positive COVID-19 results does not negatively affect early patient survival, though little information regarding donor COVID-19 organ involvement is known. While transplantation is feasible, more information regarding COVID-19-positive donor selection is needed.
Topics: COVID-19; COVID-19 Testing; Graft Survival; Humans; Organ Transplantation; Pandemics; Tissue Donors; Tissue and Organ Procurement
PubMed: 35822320
DOI: 10.1111/ajt.17145 -
Cells Sep 2023Organ transplantation remains the only treatment option for patients with end-stage organ dysfunction. However, there are numerous limitations that challenge its... (Review)
Review
Organ transplantation remains the only treatment option for patients with end-stage organ dysfunction. However, there are numerous limitations that challenge its clinical application, including the shortage of organ donations, the quality of donated organs, injury during organ preservation and reperfusion, primary and chronic graft dysfunction, acute and chronic rejection, infection, and carcinogenesis in post-transplantation patients. Acute and chronic inflammation and cell death are two major underlying mechanisms for graft injury. Necroptosis is a type of programmed cell death involved in many diseases and has been studied in the setting of all major solid organ transplants, including the kidney, heart, liver, and lung. It is determined by the underlying donor organ conditions (e.g., age, alcohol consumption, fatty liver, hemorrhage shock, donation after circulatory death, etc.), preservation conditions and reperfusion, and allograft rejection. The specific molecular mechanisms of necroptosis have been uncovered in the organ transplantation setting, and potential targeting drugs have been identified. We hope this review article will promote more clinical research to determine the role of necroptosis and other types of programmed cell death in solid organ transplantation to alleviate the clinical burden of ischemia-reperfusion injury and graft rejection.
PubMed: 37759518
DOI: 10.3390/cells12182296 -
Vaccines Aug 2022Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event... (Review)
Review
BACKGROUND
Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event that leads to the cascade of events that result in rejection of a transplanted organ.
OBJECTIVES
To describe the results of a systematic review for solid organ rejections following SARS-CoV-2 vaccination or COVID-19 infection.
METHODS
For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines for studies on the incidence of solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection, published from 1 December 2019 to 31 May 2022, with English language restriction.
RESULTS
One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). The median or mean patient age ranged from 23 to 94 years across the studies. The majority of the patients were male ( = 51, 53.1%) and were of White (Caucasian) ( = 51, 53.7%) and Hispanic ( = 15, 15.8%) ethnicity. A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination [Pfizer-BioNTech ( = 31), Moderna ( = 14), Oxford Uni-AstraZeneca ( = 10) and Sinovac-CoronaVac ( = 1)]. The median time from SARS-CoV-2 vaccination to organ rejection was 13.5 h (IQR, 3.2-17.2), while the median time from COVID-19 infection to organ rejection was 14 h (IQR, 5-21). Most patients were easily treated without any serious complications, recovered and did not require long-term allograft rejection therapy [graft success ( = 70, 85.4%), graft failure ( = 12, 14.6%), survived ( = 90, 95.7%) and died ( = 4, 4.3%)].
CONCLUSION
The reported evidence of solid organ rejections post-SARS-CoV-2 vaccination or COIVD-19 infection should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively small in relation to the hundreds of millions of vaccinations that have occurred, and the protective benefits offered by SARS-CoV-2 vaccination far outweigh the risks.
PubMed: 36016180
DOI: 10.3390/vaccines10081289 -
Pediatric Transplantation Jun 2023Understanding the role of substance use is important in the equitable allocation of solid organs and may present an opportunity for improving outcomes among substance... (Review)
Review
BACKGROUND
Understanding the role of substance use is important in the equitable allocation of solid organs and may present an opportunity for improving outcomes among substance users who receive transplants. This scoping review presents findings related to substance use among pediatric and young adult transplant populations and suggests future directions.
METHODS
A scoping review was conducted seeking studies related to substance use in pediatric and young adult transplant populations under the age of 39 years. Studies were deemed eligible if they collected data or addressed policy concerns and participants' mean age was below 39 years.
RESULTS
Twenty-nine studies were identified as eligible for this review. Overall, policies around substance use are largely inconsistent throughout both pediatric and adult transplant centers. Findings indicated that substance use among pediatric and young adult transplant recipients is similar to or lower than healthy peers. Few studies addressed marijuana use and opioid misuse, among other substances.
CONCLUSIONS
There is a general dearth of research on substance use in this population. The current findings suggest that substance use, although relatively less common, affects eligibility for transplant, may lead to poor outcomes, and affects medication adherence. Inconsistent substance use policies in transplant centers have the potential to result in bias. However, more research is needed on the effects of substance use among pediatric and young adult transplant candidates and recipients as well as on equitable policies for organ allocation for individuals who use substances.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Organ Transplantation; Transplant Recipients; Opioid-Related Disorders
PubMed: 36895133
DOI: 10.1111/petr.14497