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Journal of the Chinese Medical... Aug 2015The epithelial-mesenchymal transition (EMT) process plays pivotal roles in regulatory mechanisms of embryogenesis and wound healing physiologically, and organ fibrosis,... (Review)
Review
The epithelial-mesenchymal transition (EMT) process plays pivotal roles in regulatory mechanisms of embryogenesis and wound healing physiologically, and organ fibrosis, cancer progression, and metastasis pathologically. EMT is classified as primary, secondary, and tertiary during embryonic development. EMT contributes to repair of tissue injury and fibrogenesis by re-epithelialization and regeneration of fibroblasts, respectively. The hallmarks of EMT include loss of contact inhibition, remodeling of extracellular matrix, and reorganization of cytoskeleton, along with expression of mesenchymal markers and reduction of epithelial markers. Cancer cells acquire stemness, migration and invasive capability, evade apoptosis, and initiate metastasis to distant organs. Several EMT regulators including Snail, Zeb1, Zeb2, and Twist in solid tumor and Sox4, distal-less homeobox gene 4 (DLX4), Prdm14, Bmi1, and the forkhead box family in hematological malignancy are reviewed with regard to their signaling pathways, regulatory mechanisms, and clinical interactions.
Topics: Cell Cycle; DNA Repair; Epithelial-Mesenchymal Transition; Forkhead Box Protein M1; Hematologic Neoplasms; Humans; Neoplasms; Polycomb Repressive Complex 1; Signal Transduction; Snail Family Transcription Factors; Twist-Related Protein 1
PubMed: 26078096
DOI: 10.1016/j.jcma.2015.05.002 -
American Journal of Transplantation :... Sep 2016Across the globe, there is a shortage of donor organs for patients with end-stage organ disease. In most countries, organ donation is stagnant. Over the years, different...
Across the globe, there is a shortage of donor organs for patients with end-stage organ disease. In most countries, organ donation is stagnant. Over the years, different approaches have been attempted with variable success. Most have focused on media appeals to encourage organ donation. A more direct means to try to improve organ donation would be to reward individuals who either agree to donate (in the event of their brain death) or authorized donation of their next-of-kin. For example, in Singapore (which has an ‘opt out’ organ donation system, whereby, all citizens are considered eligible for donation unless they formally ‘opt out’ of consideration), priority for transplant is given to individuals who have not opted out (1). A different system was recently implemented in Israel where citizens were rewarded for either donor registration or authorizing donation for their next-of-kin. Israel, like most countries has an ‘opt in’ donation system whereby organ donation is not presumed and requires specific authorization by registration of the individual (prior to brain death) or authorization by next-of-kin. Specifically, the Israeli law provided two incentives: 1) patients waitlisted for solid-organ transplant who had previously registered as an organ donor ≥ 3 years before listing received higher transplant priority; and 2) first-degree relatives of individuals who either donated an organ while alive or authorized donation for their next-of-kin were granted higher transplant priority. Stoler et al. reviewed changes in organ donation before and after implementation of this novel national policy (2).
Topics: Humans; Motivation; Tissue Donors; Tissue and Organ Procurement
PubMed: 27137135
DOI: 10.1111/ajt.13850 -
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 -
Frontiers in Bioengineering and... 2022Insights into the use of cellular therapeutics, extracellular vesicles (EVs), and tissue engineering strategies for regenerative medicine applications are continually... (Review)
Review
Insights into the use of cellular therapeutics, extracellular vesicles (EVs), and tissue engineering strategies for regenerative medicine applications are continually emerging with a focus on personalized, patient-specific treatments. Multiple pre-clinical and clinical trials have demonstrated the strong potential of cellular therapies, such as stem cells, immune cells, and EVs, to modulate inflammatory immune responses and promote neoangiogenic regeneration in diseased organs, damaged grafts, and inflammatory diseases, including COVID-19. Over 5,000 registered clinical trials on ClinicalTrials.gov involve stem cell therapies across various organs such as lung, kidney, heart, and liver, among other applications. A vast majority of stem cell clinical trials have been focused on these therapies' safety and effectiveness. Advances in our understanding of stem cell heterogeneity, dosage specificity, and manipulation of stem cell activity have shed light on the potential benefits of cellular therapies and supported expansion into clinical indications such as optimizing organ preservation before transplantation. Standardization of manufacturing protocols of tissue-engineered grafts is a critical first step towards the ultimate goal of whole organ engineering. Although various challenges and uncertainties are present in applying cellular and tissue engineering therapies, these fields' prospect remains promising for customized patient-specific treatments. Here we will review novel regenerative medicine applications involving cellular therapies, EVs, and tissue-engineered constructs currently investigated in the clinic to mitigate diseases and possible use of cellular therapeutics for solid organ transplantation. We will discuss how these strategies may help advance the therapeutic potential of regenerative and transplant medicine.
PubMed: 36507264
DOI: 10.3389/fbioe.2022.942750 -
American Journal of Transplantation :... Dec 2020As the incidence of ischemia-reperfusion (I-R) injury has substantially increased, there is a pressing need to develop effective strategies to treat this global health... (Review)
Review
As the incidence of ischemia-reperfusion (I-R) injury has substantially increased, there is a pressing need to develop effective strategies to treat this global health issue. I-R injury can affect all organs and is associated with high morbidity and mortality rates. Pathological settings such as myocardial infarction, stroke, hemorrhagic shock, and solid organ transplant are particularly prone to cause I-R injury. Ischemia (hypoxia) and/or reperfusion (reoxygenation) induces various forms of cellular and structural damage. A major cause of damage is local inflammatory responses, which may spread to produce more advanced systemic inflammation. Management of I-R injury relies primarily on supportive measures, as specific treatment strategies are lacking. Extracellular vesicles (EVs) are cell-secreted nano-scale structures containing various biomolecules involved in cell communication and multiple physiological processes. EVs derived from certain cell types have been shown to exhibit anti-inflammatory, antioxidant, and angiogenic properties. This review provides an overview of EV-based therapeutics for I-R injury in kidneys, liver, heart, lungs, and brain. Additionally, the mechanisms by which EVs protect against I-R injury are discussed. Promising preclinical findings highlight the potential clinical use of EVs for I-R injury.
Topics: Acute Kidney Injury; Extracellular Vesicles; Humans; Kidney; Mesenchymal Stem Cells; Reperfusion Injury
PubMed: 32594616
DOI: 10.1111/ajt.16164 -
Experimental and Clinical... Dec 2021In India, organ donation and transplant activities are managed under the National Organ and Tissue Transplant Organisation, established per the mandate of the...
OBJECTIVES
In India, organ donation and transplant activities are managed under the National Organ and Tissue Transplant Organisation, established per the mandate of the Transplantation of Human Organs and Tissues Act 1994, as stipulated by World Health Organization guidelines.
MATERIALS AND METHODS
The National Organ and Tissue Transplant Organisation reached out to various hospitals and concerned authorities at national, regional, and local levels through E-mails and telephone calls to gather and to analyze 2019 data regarding the World Health Organization-Global Observatory on Donation and Transplantation questionnaire.
RESULTS
In 2019, India had 550 transplant centers registered with state-appropriate authorities and 140 nontransplant organ retrieval centers. Most living donors were kidney donors (8613) or liver donors (1993). Of all solid-organ transplants, most were kidney transplants, followed by liver, heart, lung, and pancreas. There were few heart and pancreas transplants in 2019, with higher percentage of female donors (65.4% and 54.3%, respectively, n = 5633 and 1084). Of transplant procedures, there were more living donor transplants (84%, n = 10 600) than deceased donor transplants (16%, n = 2023). Among all organs, wait lists for kidney transplants were higher than for other organs.
CONCLUSIONS
Reporting on organ donation and transplant of 2019 from the National Organ and Tissue Transplant Organisation, India's national registry, continued in 2020 despite the challenges of COVID-19. India has been submitting organ donation and transplant data at the national level to the Global Observatory on Donation and Transplantation consistently from 2013 to 2019 and is the only country in the World Health Organization South-East Asia Region to have done so, providing information from all states and union territories in India.
Topics: Female; Humans; Living Donors; Male; Organ Transplantation; Tissue Donors; Tissue and Organ Procurement; Treatment Outcome
PubMed: 34763630
DOI: 10.6002/ect.2021.0105 -
American Journal of Transplantation :... Dec 2022The use of extended criteria donor grafts is a promising strategy to increase the number of organ transplantations and reduce waitlist mortality. However, these organs... (Review)
Review
The use of extended criteria donor grafts is a promising strategy to increase the number of organ transplantations and reduce waitlist mortality. However, these organs are often compromised and/or damaged, are more susceptible to preservation injury, and are at risk for developing post-transplant complications. Ex vivo organ perfusion is a novel technology to preserve donor organs while providing oxygen and nutrients at distinct perfusion temperatures. This preservation method allows to resuscitate grafts and optimize function with therapeutic interventions prior to solid organ transplantation. Stem cell-based therapies are increasingly explored for their ability to promote regeneration and reduce the inflammatory response associated with in vivo reperfusion. The aim of this review is to describe the current state of stem cell-based therapies during ex vivo organ perfusion for the kidney, liver, lung, and heart. We discuss different strategies, including type of cells, route of administration, mechanisms of action, efficacy, and safety. The progress made within lung transplantation justifies the initiation of clinical trials, whereas more research is likely required for the kidney, liver, and heart to progress into clinical application. We emphasize the need for standardization of methodology to increase comparability between future (clinical) studies.
Topics: Humans; Organ Preservation; Perfusion; Organ Transplantation; Extracorporeal Circulation; Stem Cells; Reperfusion Injury
PubMed: 35896477
DOI: 10.1111/ajt.17161 -
Current Opinion in Organ Transplantation Oct 2022Older donors have the potential to close the gap between demand and supply in solid organs transplantation. Utilizing older organs, at the same time, has been associated... (Review)
Review
PURPOSE OF REVIEW
Older donors have the potential to close the gap between demand and supply in solid organs transplantation. Utilizing older organs, at the same time, has been associated with worse short- and long-term outcomes. Here, we introduce potential mechanisms on how treatments during machine perfusion (MP) may safely improve the utilization of older organs.
RECENT FINDINGS
Consequences of ischemia reperfusion injury (IRI), a process of acute, sterile inflammation leading to organ injury are more prominent in older organs. Of relevance, organ age and IRI seem to act synergistically, leading to an increase of damage associated molecular patterns that trigger innate and adaptive immune responses. While cold storage has traditionally been considered the standard of care in organ preservation, accumulating data support that both hypothermic and normothermic MP improve organ quality, particularly in older organs. Furthermore, MP provides the opportunity to assess the quality of organs while adding therapeutic agents. Experimental data have already demonstrated the potential of applying treatments during MP. New experimental show that the depletion of senescent cells that accumulate in old organs improves organ quality and transplant outcomes.
SUMMARY
As the importance of expanding the donor pool is increasing, MP and novel treatments bear the potential to assess and regenerate older organs, narrowing the gap between demand and supply.
Topics: Aged; Humans; Organ Preservation; Organ Transplantation; Perfusion; Senotherapeutics; Tissue Donors
PubMed: 35950886
DOI: 10.1097/MOT.0000000000001019 -
International Journal of Molecular... Feb 2021Solid organ transplantation is a gold standard treatment for patients suffering from an end-stage organ disease. Patient and graft survival have vastly improved during... (Review)
Review
Solid organ transplantation is a gold standard treatment for patients suffering from an end-stage organ disease. Patient and graft survival have vastly improved during the last couple of decades; however, the field of transplantation still encounters several unique challenges, such as a shortage of transplantable organs and increasing pool of extended criteria donor (ECD) organs, which are extremely prone to ischemia-reperfusion injury (IRI), risk of graft rejection and challenges in immune regulation. Moreover, accurate and specific biomarkers, which can timely predict allograft dysfunction and/or rejection, are lacking. The essential amino acid tryptophan and, especially, its metabolites via the kynurenine pathway has been widely studied as a contributor and a therapeutic target in various diseases, such as neuropsychiatric, autoimmune disorders, allergies, infections and malignancies. The tryptophan-kynurenine pathway has also gained interest in solid organ transplantation and a variety of experimental studies investigating its role both in IRI and immune regulation after allograft implantation was first published. In this review, the current evidence regarding the role of tryptophan and its metabolites in solid organ transplantation is presented, giving insights into molecular mechanisms and into therapeutic and diagnostic/prognostic possibilities.
Topics: Animals; Biomarkers; Graft Rejection; Graft Survival; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenine; Organ Transplantation; Reperfusion Injury; Transplantation, Homologous; Tryptophan
PubMed: 33671985
DOI: 10.3390/ijms22041921 -
JAMA Internal Medicine Jan 2023Large-scale motorcycle rallies attract thousands of attendees and are associated with increased trauma-related morbidity and mortality.
IMPORTANCE
Large-scale motorcycle rallies attract thousands of attendees and are associated with increased trauma-related morbidity and mortality.
OBJECTIVE
To examine the association of major US motorcycle rallies with the incidence of organ donation and transplants.
DESIGN, SETTING, AND PARTICIPANTS
This population-based, retrospective cross-sectional study used data from the Scientific Registry of Transplant Recipients for deceased organ donors aged 16 years or older involved in a motor vehicle crash and recipients of organs from these donors from March 2005 to September 2021.
EXPOSURE
Dates of 7 large US motorcycle rallies and regions near these events.
MAIN OUTCOMES AND MEASURES
The main outcomes were incidence of motor vehicle crash-related organ donation and number of patients receiving a solid organ transplant from these donors. An event study design was used to estimate adjusted rates of organ donation during the dates of 7 major US motorcycle rallies compared with the 4 weeks before and after the rallies in rally-affected and rally-unaffected (control) regions. Donor and recipient characteristics and metrics of organ quality were compared between rally and nonrally dates.
RESULTS
The study included 10 798 organ donors (70.9% male; mean [SD] age, 32.5 [13.7] years) and 35 329 recipients of these organs (64.0% male; 49.3 [15.5] years). During the rally dates, there were 406 organ donors and 1400 transplant recipients. During the 4 weeks before and after the rallies, there were 2332 organ donors and 7714 transplant recipients. Donors and recipients during rally and nonrally dates were similar in demographic and clinical characteristics, measures of organ quality, measures of recipient disease severity, and recipient waiting time. During rallies, there were 21% more organ donors per day (incidence rate ratio [IRR], 1.21; 95% CI, 1.09-1.35; P = .001) and 26% more transplant recipients per day (IRR, 1.26; 95% CI, 1.12-1.42; P < .001) compared with the 4 weeks before and after the rallies in the regions where they were held.
CONCLUSIONS AND RELEVANCE
In this cross-sectional study, major motorcycle rallies in the US were associated with increased incidence of organ donation and transplants. While safety measures to minimize morbidity and mortality during motorcycle rallies should be prioritized, this study showed the downstream association of these events with organ donation and transplants.
Topics: Humans; Male; Adult; Female; Retrospective Studies; Cross-Sectional Studies; Motorcycles; Organ Transplantation; Tissue and Organ Procurement; Tissue Donors; Registries
PubMed: 36441514
DOI: 10.1001/jamainternmed.2022.5431