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Cells Feb 2020Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently,... (Review)
Review
Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently, the therapeutic potential of EVs has been shown to extend to the field of solid organ transplantations. Mesenchymal stromal cell-derived EVs (MSC-EVs) in particular have been proposed as a new tool to improve graft survival, thanks to the modulation of tolerance toward the graft, and to their anti-fibrotic and pro-angiogenic effects. Moreover, MSC-EVs may reduce ischemia reperfusion injury, improving the recovery from acute damage. In addition, EVs currently considered helpful tools for preserving donor organs when administered before transplant in the context of hypothermic or normothermic perfusion machines. The addition of EVs to the perfusion solution, recently proposed for kidney, lung, and liver grafts, resulted in the amelioration of donor organ viability and functionality. EVs may therefore be of therapeutic interest in different aspects of the transplantation process for increasing the number of available organs and improving their long-term survival.
Topics: Animals; Extracellular Vesicles; Graft vs Host Disease; Humans; Organ Transplantation; Perfusion; Regenerative Medicine; Stem Cells
PubMed: 32033489
DOI: 10.3390/cells9020369 -
Transplantation Oct 2018Solid organ transplantation is a valid treatment option for selected patients with organ failure due to an underlying telomeropathy; however, the feasibility of... (Review)
Review
BACKGROUND
Solid organ transplantation is a valid treatment option for selected patients with organ failure due to an underlying telomeropathy; however, the feasibility of multiple-organ transplantation if several organs are compromised is unclear.
METHODS
We describe 2 patients with telomeropathy due to heterozygous telomerase RNA component or telomerase reverse transcriptase mutation, who successfully underwent serial or combined liver and lung transplantation for concurrent liver fibrosis/cirrhosis and pulmonary fibrosis.
RESULTS
Despite a challenging posttransplant course, long-term outcomes were favorable, with both patients doing fine now, respectively, 12/20 and 24 months after multiple-organ transplantation.
CONCLUSIONS
To our knowledge, this is the first report of multiple solid organ transplantation in documented telomeropathy. These cases highlight current difficulties of timely diagnosis, therapeutic approach, and postoperative complications in telomeropathy patients in whom several organs are affected.
Topics: Adult; Humans; Liver; Liver Cirrhosis; Liver Function Tests; Lung; Male; Middle Aged; Multiple Organ Failure; Organ Transplantation; Postoperative Complications; Pulmonary Fibrosis; RNA; Respiratory Function Tests; Telomerase; Telomere Homeostasis; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 29596117
DOI: 10.1097/TP.0000000000002198 -
Annual Review of Medicine Jan 2024Despite significant advances in the field of transplantation in the past two decades, current clinically available therapeutic options for immunomodulation remain fairly... (Review)
Review
Despite significant advances in the field of transplantation in the past two decades, current clinically available therapeutic options for immunomodulation remain fairly limited. The advent of calcineurin inhibitor-based immunosuppression has led to significant success in improving short-term graft survival; however, improvements in long-term graft survival have stalled. Solid organ transplantation provides a unique opportunity for immunomodulation of both the donor organ prior to implantation and the recipient post transplantation. Furthermore, therapies beyond targeting the adaptive immune system have the potential to ameliorate ischemic injury to the allograft and halt its aging process, augment its repair, and promote recipient immune tolerance. Other recent advances include expanding the donor pool by reducing organ discard, and bioengineering and genetically modifying organs from other species to generate transplantable organs. Therapies discussed here will likely be most impactful if individualized on the basis of specific donor and recipient considerations.
Topics: Humans; Immunomodulation; Immune Tolerance; Bioengineering; Graft Survival; Organ Transplantation
PubMed: 37562417
DOI: 10.1146/annurev-med-050522-034012 -
Current Opinion in Organ Transplantation Apr 2020The development and implementation of 'increased risk donor' (IRD) status by the Centers for Disease Control (CDC) was intended to guide patients and providers in... (Review)
Review
PURPOSE OF REVIEW
The development and implementation of 'increased risk donor' (IRD) status by the Centers for Disease Control (CDC) was intended to guide patients and providers in decision making regarding risk of infectious transmission via solid organ transplantation. Several contemporary studies have shown underutilization of these organs. This review summarizes the issues surrounding IRD status as well as recent advances in our understanding of the risks and benefits of increased risk organs and their appropriate utilization.
RECENT FINDINGS
Risk of window-period infection remains exceedingly low, and implementation of nucleic acid testing for HIV and hepatitis C virus (HCV) has resulted in decreasing risk of window-period infection often by an order of magnitude or more. Surgeons remain hesitant to utilize IRD organs. In addition, surgeon assessment of risk by donor behaviour was often discordant with known risks of those behaviours. Studies investigating outcomes of utilization of IRD organs suggest long-term mortality and graft survival is at least equivalent to non-IRD organs. Contemporary results suggest that IRD organs continue to be underutilized, particularly adult kidneys and lungs, with hundreds of wasted organs per year.
SUMMARY
CDC IRD labelling has led to an underutilization of organs for transplantation. The risks associated with acceptance of an IRD organ are inflated by surgeons and patients, and outcomes for patients who undergo transplantation with increased risk organs are similar to or better than those for patients whom accept standard risk organs. The rate of transmission of window-period infection from IRD organs is exceptionally low. The harms regarding the utility of Public Health Service increased risk classification outweigh the benefits for patients in need of transplant.
Topics: Humans; Organ Transplantation; Risk Factors; Tissue Donors
PubMed: 32073497
DOI: 10.1097/MOT.0000000000000735 -
Lupus Nov 2015Antiphospholipid syndrome is considered a high risk factor for any kind of surgery. Considering that all solid organ transplants are critically dependent on the patency... (Review)
Review
Antiphospholipid syndrome is considered a high risk factor for any kind of surgery. Considering that all solid organ transplants are critically dependent on the patency of vascular anastomosis, there is much concern about the consequences this pro-thrombotic condition may have on transplantation. Relatively little information is available in the literature assessing the real risk that antiphospholipid syndrome or the presence of antiphospholipid antibodies represent in solid organ transplantation. The aim of this article is to review the literature related to transplantation of solid organs in patients diagnosed with antiphospholipid syndrome or patients with positive antiphospholipid antibodies.
Topics: Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Female; Humans; Lupus Coagulation Inhibitor; Middle Aged; Organ Transplantation; Risk Factors; Thrombophilia; Thrombosis; Transplantation Immunology; Treatment Outcome
PubMed: 26162685
DOI: 10.1177/0961203315595129 -
Radiologic Technology 2012Medical imaging plays a key role in solid organ donation and transplantation. In addition to confirming the clinical diagnosis of brain death, imaging examinations are... (Review)
Review
Medical imaging plays a key role in solid organ donation and transplantation. In addition to confirming the clinical diagnosis of brain death, imaging examinations are used to assess potential organ donors and recipients, evaluate donated organs, and monitor transplantation outcomes. This article introduces the history, biology, ethics, and institutions of organ donation and transplantation medicine. The article also discusses current and emerging imaging applications in the transplantation field and the controversial role of neuroimaging to confirm clinically diagnosed brain death.
Topics: Brain Death; Diagnostic Imaging; Electroencephalography; Humans; Informed Consent; Neuroimaging; Organ Transplantation; Patient Selection; Postoperative Complications; Tissue Donors; Tissue and Organ Procurement
PubMed: 22461345
DOI: No ID Found -
Current Opinion in Infectious Diseases Aug 2019Adenoviruses are an important cause of morbidity and mortality of solid organ transplant patients and remain a clinical challenge with regard to diagnosis and treatment.... (Review)
Review
PURPOSE OF REVIEW
Adenoviruses are an important cause of morbidity and mortality of solid organ transplant patients and remain a clinical challenge with regard to diagnosis and treatment. In this review, we provide an approach to identification and classification of adenovirus infection and disease, highlight risk factors, and outline management options for adenovirus disease in solid organ transplant patients.
RECENT FINDINGS
Additional clinical data and pathologic findings of adenovirus disease in different organs and transplant recipients are known. Unlike hematopoietic cell transplant recipients, adenovirus blood PCR surveillance and preemptive therapy is not supported in solid organ transplantation. Strategies for management of adenovirus disease continue to evolve with newer antivirals, such as brincidofovir and adjunctive immunotherapies, but more studies are needed to support their use.
SUMMARY
Distinguishing between adenovirus infection and disease is an important aspect in adenovirus management as treatment is warranted only in symptomatic solid organ transplant patients. Supportive care and decreasing immunosuppression remain the mainstays of management. Cidofovir remains the antiviral of choice for severe or disseminated disease. Given its significant nephrotoxic effect, administration of probenecid and isotonic saline precidofovir and postcidofovir infusion is recommended.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Antiviral Agents; DNA, Viral; Diagnosis, Differential; Disease Management; Disease Susceptibility; Humans; Immunocompromised Host; Organ Transplantation; Polymerase Chain Reaction; Public Health Surveillance; Risk Factors; Transplant Recipients; Treatment Outcome
PubMed: 31116132
DOI: 10.1097/QCO.0000000000000558 -
Journal of Clinical Tuberculosis and... Aug 2016Non-tuberculous mycobacteria are ubiquitous environmental organisms that are now increasingly recognized as important causes of clinical disease in solid organ... (Review)
Review
Non-tuberculous mycobacteria are ubiquitous environmental organisms that are now increasingly recognized as important causes of clinical disease in solid organ transplant recipients. Risk factors of non-tuberculous mycobacteria infection are severe immunologic defects and structural abnormalities. Lung transplant recipients are at higher risk for non-tuberculous mycobacterial disease compared to recipients of other solid organs. The clinical presentation could be skin and soft tissue infection, osteoarticular disease, pleuropulmonary infection, bloodstream (including catheter-associated) infection, lymphadenitis, and disseminated or multi-organ disease. Management of non-tuberculous mycobacteria infection is complex due to the prolonged treatment course with multi-drug regimens that are anticipated to interact with immunosuppressive medications. This review article provides an update on infections due to non-tuberculous mycobacteria after solid organ transplantation, and discusses the epidemiology, risk factors, clinical presentation, and management.
PubMed: 31723683
DOI: 10.1016/j.jctube.2016.04.001 -
Cell and Tissue Research Apr 2021Organ preservation is a prerequisite for an urgent increase in the availability of organs for solid organ transplantation (SOT). An increasing amount of expanded... (Review)
Review
Organ preservation is a prerequisite for an urgent increase in the availability of organs for solid organ transplantation (SOT). An increasing amount of expanded criteria donor (ECD) organs are used clinically. Currently, the paradigm of organ preservation is shifting from simple reduction of cellular metabolic activity to maximal simulation of an ex vivo physiological microenvironment. An ideal organ preservation technique should not only preserve isolated organs but also offer the possibility of rehabilitation and evaluation of organ function prior to transplantation. Based on the fact that mesenchymal stromal cells (MSCs) possess strong regeneration properties, the combination of MSCs with machine perfusion (MP) is expected to be superior to conventional preservation methods. In recent years, several studies have attempted to use this strategy for SOT showing promising outcomes. With better organ function during ex vivo preservation and the potential of utilization of organs previously deemed untransplantable, this strategy is meaningful for patients with organ failure to help overcome organ shortage in the field of SOT.
Topics: Humans; Mesenchymal Stem Cells; Organ Preservation; Organ Transplantation; Perfusion; Regenerative Medicine
PubMed: 33439348
DOI: 10.1007/s00441-020-03406-3 -
Nature Reviews. Cancer Apr 2021The extracellular matrix is a fundamental, core component of all tissues and organs, and is essential for the existence of multicellular organisms. From the earliest... (Review)
Review
The extracellular matrix is a fundamental, core component of all tissues and organs, and is essential for the existence of multicellular organisms. From the earliest stages of organism development until death, it regulates and fine-tunes every cellular process in the body. In cancer, the extracellular matrix is altered at the biochemical, biomechanical, architectural and topographical levels, and recent years have seen an exponential increase in the study and recognition of the importance of the matrix in solid tumours. Coupled with the advancement of new technologies to study various elements of the matrix and cell-matrix interactions, we are also beginning to see the deployment of matrix-centric, stromal targeting cancer therapies. This Review touches on many of the facets of matrix biology in solid cancers, including breast, pancreatic and lung cancer, with the aim of highlighting some of the emerging interactions of the matrix and influences that the matrix has on tumour onset, progression and metastatic dissemination, before summarizing the ongoing work in the field aimed at developing therapies to co-target the matrix in cancer and cancer metastasis.
Topics: ADAM Proteins; ADAMTS Proteins; Bone Morphogenetic Protein 1; Cathepsins; Cell Movement; Collagen; Cystatins; Elastin; Extracellular Matrix; Extracellular Matrix Proteins; Fibrillins; Glucuronidase; Glycoproteins; Humans; Hyaluronoglucosaminidase; Matrix Metalloproteinases; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Protein Processing, Post-Translational; Proteoglycans; Serpins; Tissue Inhibitor of Metalloproteinases; Tolloid-Like Metalloproteinases; Tumor Microenvironment
PubMed: 33589810
DOI: 10.1038/s41568-020-00329-7