Tissue‐Specific Isolation of Hepatocyte Extracellular Vesicles From Human Plasma Enables Tissue‐Resolved Proteomic and miRNA Profiling
- 1Mursla Bio
- 2University College London
Abstract
Tissue‐specific resolution remains a critical barrier in liquid biopsy for precision medicine. To address this, we developed NEXPLOR (Novel EXtracellular vesicle PopuLation Omics Revealer), an immunoaffinity platform enabling selective enrichment of circulating tissue‐specific extracellular vesicles (TS‐EVs), demonstrated here for liver‐derived hepatocyte‐EVs (h‐EVs). Through in silico discovery and orthogonal antibody validation across tissues, we identified a four‐marker panel (ASGR1, ASGR2, TFR2, SLCO1B1) that selectively enriched hepatocyte EVs without co‐capturing the dominant platelet‐ and leukocyte‐EV background. In a clinical cohort of hepatocellular carcinoma (HCC), non‐cancer cirrhosis and healthy donors, NEXPLOR recovered 57% more proteins than bulk EV isolation, with greater reproducibility. By restoring tissue context, h‐EVs exposed liver biology that bulk EVs miss, spanning three levels: metabolic pathways (carbon metabolism, HIF‐1α signalling, ferroptosis), HCC‐defining proteins (PGD, H2AZ1, PRDX5), and progression‐tracking candidates (CFB, PCSK9). Small RNA sequencing detected five miRNAs upregulated in HCC versus cirrhosis h‐EVs, against 21 in bulk EVs (no overlap); yet only the h‐EV miRNAs mapped to HCC‐relevant signalling, and hepatocyte‐regulatory miR‐124‐3p appeared exclusively in h‐EVs. Together, these results establish tissue‐specific EV enrichment as a route to more actionable, multi‐omic liquid biopsies in HCC, cirrhosis and other diseases in urgent need of non‐invasive biomarkers for patient diagnosis, monitoring and stratification.
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BibTeX
@article{figueiras2026tissuespecific,
title = {{Tissue‐Specific Isolation of Hepatocyte Extracellular Vesicles From Human Plasma Enables Tissue‐Resolved Proteomic and miRNA Profiling}},
author = {Ricardo Figueiras and Susana Vagueiro and Raissa Kay and Elnaz Persia and Roger de Alwis and Razan Hijazi and Brian Davidson and Kristine von Bargen and Pierre Arsène and Tomás Dias},
journal = {Journal of extracellular vesicles},
year = {2026},
month = oct,
doi = {10.1002/jev2.70372},
url = {https://europepmc.org/article/PMC/PMC13653647},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Tissue‐Specific Isolation of Hepatocyte Extracellular Vesicles From Human Plasma Enables Tissue‐Resolved Proteomic and miRNA Profiling
AU - Ricardo Figueiras
AU - Susana Vagueiro
AU - Raissa Kay
AU - Elnaz Persia
AU - Roger de Alwis
AU - Razan Hijazi
AU - Brian Davidson
AU - Kristine von Bargen
AU - Pierre Arsène
AU - Tomás Dias
PY - 2026
DA - 2026/10/01
JO - Journal of extracellular vesicles
DO - 10.1002/jev2.70372
UR - https://europepmc.org/article/PMC/PMC13653647
AB - Tissue‐specific resolution remains a critical barrier in liquid biopsy for precision medicine. To address this, we developed NEXPLOR (Novel EXtracellular vesicle PopuLation Omics Revealer), an immunoaffinity platform enabling selective enrichment of circulating tissue‐specific extracellular vesicles (TS‐EVs), demonstrated here for liver‐derived hepatocyte‐EVs (h‐EVs). Through in silico discovery and orthogonal antibody validation across tissues, we identified a four‐marker panel (ASGR1, ASGR2, TFR2, SLCO1B1) that selectively enriched hepatocyte EVs without co‐capturing the dominant platelet‐ and leukocyte‐EV background. In a clinical cohort of hepatocellular carcinoma (HCC), non‐cancer cirrhosis and healthy donors, NEXPLOR recovered 57% more proteins than bulk EV isolation, with greater reproducibility. By restoring tissue context, h‐EVs exposed liver biology that bulk EVs miss, spanning three levels: metabolic pathways (carbon metabolism, HIF‐1α signalling, ferroptosis), HCC‐defining proteins (PGD, H2AZ1, PRDX5), and progression‐tracking candidates (CFB, PCSK9). Small RNA sequencing detected five miRNAs upregulated in HCC versus cirrhosis h‐EVs, against 21 in bulk EVs (no overlap); yet only the h‐EV miRNAs mapped to HCC‐relevant signalling, and hepatocyte‐regulatory miR‐124‐3p appeared exclusively in h‐EVs. Together, these results establish tissue‐specific EV enrichment as a route to more actionable, multi‐omic liquid biopsies in HCC, cirrhosis and other diseases in urgent need of non‐invasive biomarkers for patient diagnosis, monitoring and stratification.
SN - 2001-3078
ER -