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Transplant Immunology Jun 2022The purpose of this review is to highlight the potential role for the cluster of differentiation protein 14 (CD14), a co-receptor for toll-like receptor (TLR) signals... (Review)
Review
The purpose of this review is to highlight the potential role for the cluster of differentiation protein 14 (CD14), a co-receptor for toll-like receptor (TLR) signals and as a proximal target for innate immune signals induced during procurement of solid organs for transplantation. CD14 facilitates the detection of multiple pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) by various TLRs. All solid organs used for transplantation are exposed to PAMPs and DAMPs generated during the course of procurement that inevitably trigger injurious inflammatory responses in the donor organ. Multiple experimental animal studies and observations in human organs have provided a solid rationale to consider CD14 blockade as a therapeutic target. CD14 has been recognized for over three decades to play an essential role in innate immune signals associated with sepsis. More recent data now show that genetic deletion or antibody blockade of CD14 can modify ischemic tissue injury in the kidney, liver, heart and lung. Thus, data presented in this review suggest that anti-CD14 directed therapies might be applied to organ preservation strategies in solid organ transplantation.
Topics: Animals; Kidney; Organ Preservation; Organ Transplantation; Pathogen-Associated Molecular Pattern Molecules; Toll-Like Receptors
PubMed: 35283329
DOI: 10.1016/j.trim.2022.101580 -
World Journal of Gastroenterology Jul 2019The transplanted liver can modulate the recipient immune system to induce tolerance after transplantation. This phenomenon was observed nearly five decades ago.... (Review)
Review
The transplanted liver can modulate the recipient immune system to induce tolerance after transplantation. This phenomenon was observed nearly five decades ago. Subsequently, the liver's role in multivisceral transplantation was recognized, as it has a protective role in preventing rejection of simultaneously transplanted solid organs such as kidney and heart. The liver has a unique architecture and is home to many cells involved in immunity and inflammation. After transplantation, these cells migrate from the liver into the recipient. Early studies identified chimerism as an important mechanism by which the liver modulates the human immune system. Recent studies on human T-cell subtypes, cytokine expression, and gene expression in the allograft have expanded our knowledge on the potential mechanisms underlying immunomodulation. In this article, we discuss the privileged state of liver transplantation compared to other solid organ transplantation, the liver allograft's role in multivisceral transplantation, various cells in the liver involved in immune responses, and the potential mechanisms underlying immunomodulation of host alloresponses.
Topics: Allografts; Graft Rejection; Graft Survival; Humans; Immune Tolerance; Liver; Organ Transplantation; Transplantation, Homologous
PubMed: 31333306
DOI: 10.3748/wjg.v25.i25.3123 -
Aging Feb 2022Telomeres are protective nucleoprotein structures at the end of chromosomes that shorten with age. Telomere length (TL) in peripheral blood mononuclear cells (PBMCs) has...
BACKGROUND
Telomeres are protective nucleoprotein structures at the end of chromosomes that shorten with age. Telomere length (TL) in peripheral blood mononuclear cells (PBMCs) has been proposed as surrogate marker for TL in the entire organism. Solid evidence that supports this concept is lacking.
METHODS
Relative TL (RTL) was measured in PBMCS and multiple solid tissues from 24 young (4 months) and 24 aged (14 months) Sprague-Dawley (SD) rats. The mRNA expression of telomerase (TERT) and shelterin proteins TERF-1 and TERF-2 was also measured.
RESULTS
Mean RTL in PBMCs and solid tissues of young rats ranged from 0.64 ± 0.26 in large intestine to 1.07 ± 0.22 in skeletal muscle. RTL in PBMCs correlated with that in kidney (r = 0.315, p = 0.008), skeletal muscle (r = 0.276, p = 0.022), liver (r = 0.269, p = 0.033), large intestine (r = -0.463, p = 7.035E-5) and aorta (r = -0.273, p = 0.028). A significant difference of RTL between young and aged animals was only observed in aorta (0.98 ± 0.15 vs. 0.76 ± 0.11, p = 1.987E-6), lung (0.76 ± 0.14 vs. 0.85 ± 0.14, p = 0.024) and visceral fat (0.83 ± 0.14 vs. 0.92 ± 0.15, p = 0.44). The expression of TERT significantly differed between the tested organs with highest levels in liver and kidney. Age-related differences in TERT expression were found in PBMCs, skeletal muscle, and visceral fat. mRNA expression of TERF-1 and TERF-2 was tissue-specific with the highest levels in liver. Age-related differences in TERF-1 and TERF-2 expression were inconsistent.
CONCLUSIONS
The present study questions the utility of RTL in PBMCs as a biomarker for the individual assessment of aging.
Topics: Animals; Leukocytes, Mononuclear; RNA, Messenger; Rats; Rats, Sprague-Dawley; Telomerase; Telomere
PubMed: 35220278
DOI: 10.18632/aging.203922 -
Biomaterials Research 2016Solid organ fabrication is an ultimate goal of Regenerative Medicine. Since the introduction of Tissue Engineering in 1993, functional biomaterials, stem cells, tunable... (Review)
Review
Solid organ fabrication is an ultimate goal of Regenerative Medicine. Since the introduction of Tissue Engineering in 1993, functional biomaterials, stem cells, tunable microenvironments, and high-resolution imaging technologies have significantly advanced efforts to regenerate in vitro culture or tissue platforms. Relatively simple flat or tubular organs are already in (pre)clinical trials and a few commercial products are in market. The road to more complex, high demand, solid organs including heart, kidney and lung will require substantive technical advancement. Here, we consider two emerging technologies for solid organ fabrication. One is decellularization of cadaveric organs followed by repopulation with terminally differentiated or progenitor cells. The other is 3D bioprinting to deposit cell-laden bio-inks to attain complex tissue architecture. We reviewed the development and evolution of the two technologies and evaluated relative strengths needed to produce solid organs, with special emphasis on the heart and other tissues of the cardiovascular system.
PubMed: 27583168
DOI: 10.1186/s40824-016-0074-2 -
The Yale Journal of Biology and Medicine Sep 2018In the past, a diagnosis of organ failure would essentially be a death sentence for patients. With improved techniques for organ procurement and surgical procedures,... (Review)
Review
In the past, a diagnosis of organ failure would essentially be a death sentence for patients. With improved techniques for organ procurement and surgical procedures, transplantations to treat organ failure have become standard medical practice. However, while the demand for organs has skyrocketed, the donor pool has not kept pace leading to long recipient waiting lists. Organ preservation provides a means to increase the number of available transplantable organs. However, there are significant drawbacks associated with cold storage, the current gold standard. To address the short-comings due to diffusional limitations, engineers have developed cold perfusion systems. More recently, there has been a significant trend towards the development of near-normothermic systems to enhance the functional preservation of solid organs including livers, lungs, hearts, kidneys, and vascularized composite allotransplants. Here we review recent advances in the development of perfusion systems for the preservation of solid organs. We provide a brief history of organ transplantation, the limitations of existing systems, and describe research being done to develop commercially available perfusion systems to enhance organ preservation.
Topics: Bioreactors; Humans; Mesenchymal Stem Cells; Organ Preservation
PubMed: 30258317
DOI: No ID Found -
World Journal of Transplantation Mar 2024This review aims to present the developments occurring in the field of artificial organs and particularly focuses on the presentation of developments in artificial... (Review)
Review
This review aims to present the developments occurring in the field of artificial organs and particularly focuses on the presentation of developments in artificial kidneys. The challenges for biomedical engineering involved in overcoming the potential difficulties are showcased, as well as the importance of interdisciplinary collaboration in this marriage of medicine and technology. In this review, modern artificial kidneys and the research efforts trying to provide and promise artificial kidneys are presented. But what are the problems faced by each technology and to what extent is the effort enough to date?
PubMed: 38576754
DOI: 10.5500/wjt.v14.i1.89025 -
Transplant Immunology Aug 2023Biological aging is the accumulation of cellular and molecular damage within an individual over time. The biological age of a donor organ is known to influence clinical... (Review)
Review
INTRODUCTION
Biological aging is the accumulation of cellular and molecular damage within an individual over time. The biological age of a donor organ is known to influence clinical outcomes of solid organ transplantation, including delayed graft function and frequency of rejection episodes. While much research has focused on the biological age of donor organs, the recipient's biological age may also influence transplantation outcomes. The aim of this scoping review was to identify and provide an overview of the existing evidence regarding biological aging in solid organ transplant recipients and the impact on patient outcomes post-transplant.
METHODS
Literature searches were carried out on PubMed, Web of Science, Google Scholar, Embase and TRIP using the phrases 'solid organ transplant', 'cell senescence', 'cell aging' and 'outcomes', using boolean 'and/or' phrases and MeSH terms. Duplicates were removed and abstracts were reviewed by two independent reviewers. Full papers were then screened for inclusion by two reviewers. Data extraction was carried out using a standardised proforma agreed on prior to starting.
RESULTS
32 studies, including data on a total of 7760 patients, were identified for inclusion in this review; 23 relating to kidney transplant recipients, three to liver transplant, five to lung transplant and one to heart transplantation. A wide range of biomarkers of biological aging have been assessed in kidney transplant recipients, whereas studies of liver, lung and heart transplant have predominantly assessed recipient telomere length. The most robust associations with clinical outcomes are observed in kidney transplant recipients, possibly influenced by the larger number of studies and the use of a wider range of biomarkers of biological aging. In kidney transplant recipients reduced thymic function and accumulation of terminally differentiated T cell populations was associated with reduced risk of acute rejection but increased risk of infection and mortality.
CONCLUSION
Studies to date on biological aging in transplant recipients have been heavily biased to kidney transplant recipients. The results from these studies suggest recipient biological age can influence clinical outcomes and future research is needed to prioritise robust biomarkers of biological aging in transplant recipients.
Topics: Humans; Organ Transplantation; Heart Transplantation; Liver Transplantation; Lung Transplantation; Transplant Recipients; Aging; Graft Rejection
PubMed: 37182719
DOI: 10.1016/j.trim.2023.101851 -
Bioengineering (Basel, Switzerland) Aug 2023The primary aim of this study was to analyze studies that use electrochemotherapy (ECT) in "deep-seated" tumors in solid organs (liver, kidney, bone metastasis,... (Review)
Review
The primary aim of this study was to analyze studies that use electrochemotherapy (ECT) in "deep-seated" tumors in solid organs (liver, kidney, bone metastasis, pancreas, and abdomen) and understand the similarities between patient selection, oncologic selection, and use of new procedures and technology across the organ systems to assess response rates. A literature search was conducted using the term "Electrochemotherapy" in the title field using publications from 2017 to 2023. After factoring in inclusion and exclusion criteria, 29 studies were analyzed and graded based on quality in full. The authors determined key patient and oncologic selection characteristics and ECT technology employed across organ systems that yielded overall responses, complete responses, and partial responses of the treated tumor. It was determined that key selection factors included: the ability to be administered bleomycin, life expectancy greater than three months, unrespectability of the lesion being treated, and a later stage, more advanced cancer. Regarding oncologic selection, all patient cohorts had received chemotherapy or surgery previously but had disease recurrence, making ECT the only option for further treatment. Lastly, in terms of the use of technology, the authors found that studies with better response rates used the ClinporatorTM and updated procedural guidelines by SOP. Thus, by considering patient, oncologic, and technology selection, ECT can be further improved in treating lesions in solid organs.
PubMed: 37627860
DOI: 10.3390/bioengineering10080975 -
Clinical Microbiology and Infection :... Apr 2023Solid organ transplant (SOT) recipients are at increased risks of morbidity and mortality associated with COVID-19. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Solid organ transplant (SOT) recipients are at increased risks of morbidity and mortality associated with COVID-19.
OBJECTIVES
This study aimed to evaluate the immunogenicity of COVID-19 vaccines in SOT recipients.
DATA SOURCES
Electronic databases were searched for eligible reports published from 1 December 2019 to 31 May 2022.
STUDY ELIGIBILITY CRITERIA
We included reports evaluating the humoral immune response (HIR) or cellular immune response rate in SOT recipients after the administration of COVID-19 vaccines.
PARTICIPANTS
SOT recipients who received COVID-19 vaccines.
ASSESSMENT OF RISK OF BIAS
We used the Newcastle-Ottawa scale to assess bias in case-control and cohort studies. For randomised-controlled trials, the Jadad Scale was used.
METHODS
We used a random-effects model to calculate the pooled rates of immune response with 95% CI. We used a risk ratio (RR) with 95% CI for a comparison of immune responses between SOT and healthy controls.
RESULTS
A total of 91 reports involving 11 886 transplant recipients (lung: 655; heart: 539; liver: 1946; and kidney: 8746) and 2125 healthy controls revealed pooled HIR rates after the 1st, 2nd, and 3rd COVID-19 vaccine doses in SOT recipients were 9.5% (95% CI, 7-11.9%), 43.6% (95% CI, 39.3-47.8%) and 55.1% (95% CI, 44.7-65.6%), respectively. For specific organs, the HIR rates were still low after 1st vaccine dose (lung: 4.4%; kidney: 9.4%; heart: 13.2%; liver: 29.5%) and 2nd vaccine dose (lung: 28.4%; kidney: 37.6%; heart: 50.3%; liver: 64.5%).
CONCLUSIONS
A booster vaccination enhances the immunogenicity of COVID-19 vaccines in SOT; however, a significant share of the recipients still has not built a detectable HIR after receiving the 3rd dose. This finding calls for alternative approaches, including the use of monoclonal antibodies. In addition, lung transplant recipients need urgent booster vaccination to improve the immune response.
Topics: Humans; COVID-19 Vaccines; Organ Transplantation; Transplant Recipients; COVID-19; Vaccines
PubMed: 36509376
DOI: 10.1016/j.cmi.2022.12.004 -
Clinical Microbiology and Infection :... Jun 2022The COVID-19 pandemic has influenced the field of solid organ transplantation (SOT) in many ways. COVID-19 has led to programmatic impacts and changes in donor and... (Review)
Review
BACKGROUND
The COVID-19 pandemic has influenced the field of solid organ transplantation (SOT) in many ways. COVID-19 has led to programmatic impacts and changes in donor and recipient selection. Several studies have evaluated the course, optimal treatment, and prevention of COVID-19 in SOT recipients.
OBJECTIVES
To review the literature on COVID-19 in SOT recipients.
SOURCES
PubMed, Web of Science, and Google Scholar were searched. The search was restricted to articles published between January 1, 2019 and December 1, 2021.
CONTENT
The COVID-19 pandemic initially led to a decreased volume of solid organ transplants. However, transplant volumes at most centres have rebounded. Donor selection remains an incompletely defined issue. Several reports suggest that donor-derived SARS-CoV-2 infections occur only in lung transplant recipients and that other organs from SARS-CoV-2 PCR-positive donors could potentially be safely used. However, these data are limited to case series. Transplantation for end-stage lung disease after COVID-19 infection is increasingly common and has been performed with acceptable outcomes. In acute COVID-19 in a transplant candidate, transplantation should be delayed when feasible. After adjustment, mortality after COVID-19 appear similar in SOT recipients compared to the general population, with notable increased use of antiviral and anti-inflammatory treatment options. Prevention of COVID-19 is key in SOT recipients. Vaccination of SOT recipients and anyone who is in contact with SOT recipients is one of the cornerstones of prevention. Nonpharmacological interventions such as face coverings, hand hygiene, and physical distancing remain ever important as well.
IMPLICATIONS
The COVID-19 pandemic continues to have an important impact on SOT candidates and recipients. Prevention of infection is the most important measure and requires careful attention to approaches to vaccination and messaging of the ongoing need for face coverings, physical distancing, and hand hygiene.
Topics: COVID-19; Humans; Organ Transplantation; Pandemics; SARS-CoV-2; Transplant Recipients
PubMed: 35189336
DOI: 10.1016/j.cmi.2022.02.005