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Cell-specific Extracellular Vesicles and Their miRNA Cargo Released Into the Organ Preservation Solution During Cold Ischemia Storage as Biomarkers for Liver Transplant Outcomes.
Vidal-Correoso, Daniel; Mateo, Sandra V; Muñoz-Morales, Ana M; Lucas-Ruiz, Fernando; Jover-Aguilar, Marta; Alconchel, Felipe; Martínez-Alarcón, Laura; Sánchez-Redondo, Sara; Santos, Vanesa; López-López, Víctor; Ríos-Zambudio, Antonio; Cascales, Pedro; Pons, José Antonio; Ramírez, Pablo; Pelegrín, Pablo; Peinado, Héctor; Baroja-Mazo, Alberto.
Afiliación
  • Vidal-Correoso D; Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
  • Mateo SV; Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
  • Muñoz-Morales AM; Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
  • Lucas-Ruiz F; Experimental Ophthalmology Group, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla) & Ophthalmology Department, Universidad de Murcia, Murcia, Spain.
  • Jover-Aguilar M; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Alconchel F; Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
  • Martínez-Alarcón L; Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
  • Sánchez-Redondo S; General Surgery and Abdominal Solid Organ Transplantation Unit, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain.
  • Santos V; Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
  • López-López V; Microenvironment & Metastasis Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Ríos-Zambudio A; Microenvironment & Metastasis Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Cascales P; Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
  • Pons JA; General Surgery and Abdominal Solid Organ Transplantation Unit, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain.
  • Ramírez P; Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
  • Pelegrín P; General Surgery and Abdominal Solid Organ Transplantation Unit, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain.
  • Peinado H; Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
  • Baroja-Mazo A; General Surgery and Abdominal Solid Organ Transplantation Unit, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain.
Transplantation ; 2024 Apr 05.
Article en En | MEDLINE | ID: mdl-38578699
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.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transplantation Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transplantation Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos