1. Cell-specific Extracellular Vesicles and Their miRNA Cargo Released Into the Organ Preservation Solution During Cold Ischemia Storage as Biomarkers for Liver Transplant Outcomes.
- Author
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Vidal-Correoso D, Mateo SV, Muñoz-Morales AM, Lucas-Ruiz F, Jover-Aguilar M, Alconchel F, Martínez-Alarcón L, Sánchez-Redondo S, Santos V, López-López V, Ríos-Zambudio A, Cascales P, Pons JA, Ramírez P, Pelegrín P, Peinado H, and Baroja-Mazo A
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Treatment Outcome, Aged, Graft Rejection metabolism, Graft Rejection genetics, Graft Survival, Liver Transplantation adverse effects, Extracellular Vesicles metabolism, Extracellular Vesicles transplantation, Organ Preservation Solutions, MicroRNAs metabolism, MicroRNAs genetics, Cold Ischemia adverse effects, Organ Preservation methods, Biomarkers metabolism
- Abstract
Background: Liver transplantation (LT) is crucial for end-stage liver disease patients, but organ shortages persist. Donation after circulatory death (DCD) aims to broaden the donor pool but presents challenges. Complications like acute rejection, hepatic artery thrombosis, and biliary issues still impact posttransplant prognosis. Biomarkers, including extracellular vesicles (EVs) and microRNAs (miRNAs), show promise in understanding and monitoring posttransplant events. This study explores the role of EVs and their miRNA cargo in LT, including their potential as diagnostic tools., Methods: EVs from intrahepatic end-ischemic organ preservation solution (eiOPS) in 79 donated livers were detected using different techniques (nanosight tracking analysis, transmission electron microscopy, and flow cytometry). EV-derived miRNAs were identified by quantitative real time-polymerase chain reaction. Bioinformatics analysis was performed using the R platform., Results: Different-sized and origin-specific EVs were found in eiOPS, with significantly higher concentrations in DCD compared with donation after brain death organs. Additionally, several EV-associated miRNAs, including let-7d-5p , miR-28-5p , miR-200a-3p , miR-200b-3p , miR-200c-3p , and miR-429 , were overexpressed in DCD-derived eiOPS. These miRNAs also exhibited differential expression patterns in liver tissue biopsies. Pathway analysis revealed enrichment in signaling pathways involved in extracellular matrix organization and various cellular processes. Moreover, specific EVs and miRNAs correlated with clinical outcomes, including survival and early allograft dysfunction. A predictive model combining biomarkers and clinical variables showed promise in acute rejection detection after LT., Conclusions: These findings provide new insights into the use of EVs and miRNAs as biomarkers and their possible influence on posttransplantation outcomes, potentially contributing to improved diagnostic approaches and personalized treatment strategies in LT., Competing Interests: A.B.-M., P.P., and L.M.-A. are co-founders of Viva In Vitro Diagnostics SL, a company focused on utilizing the NLR Family Pyrin Domain Containing 3 inflammasome as a disease biomarker. A.B.-M. is also co-inventor listed on a provisional patent application for an in vitro method predicting organ transplant rejection. However, it is important to note that this research was conducted independently, without any commercial or financial associations that might be considered a conflict of interest. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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