By isolating liver-derived extracellular vesicles from blood samples, researchers identified 57% more proteins than conventional methods and uncovered molecular differences between liver cancer and cirrhosis.
A peer-reviewed study published in the Journal of Extracellular Vesicles has validated a tissue-specific extracellular vesicle (TS-EV) platform designed to capture the multiomic biology of living cells from plasma samples, starting with liver tissue.
Developed by Mursla Bio, the technology underpins the company’s EvoLiver test, which has received US Food and Drug Administration Breakthrough Device designation, as well as precision medicine programs conducted with pharmaceutical partners. The study builds on findings first released as a preprint in June 2025.
“EVs are released by virtually every tissue into the bloodstream. They carry health and disease markers that can be traced back to their origin, much as a tissue biopsy would. To our knowledge, this is the most comprehensive validation to date of a platform for tissue-specific EV isolation from human plasma,” says Dr Tomás Dias, chief scientific officer of Mursla Bio, in a release.
Enriching Hepatocyte-Derived Vesicles
The study evaluated Mursla Bio’s NEXPLOR technology, which selectively enriched hepatocyte-derived EVs (h-EVs) over vesicles originating from lung, kidney, breast, adipose, and muscle tissue, as well as blood cells that predominate in plasma. Researchers analyzed the multiomic cargo of h-EVs against paired bulk EV preparations from clinical plasma samples of under 2 mL collected from healthy donors and patients diagnosed with cirrhosis or hepatocellular carcinoma (HCC).
Proteomic analysis showed that h-EVs identified 57% more proteins than bulk EV preparations, demonstrating improved reproducibility while accessing internal hepatocyte machinery. While bulk EV preparations were dominated by liver-secreted plasma proteins such as albumin, the h-EV fraction showed enrichment in mitochondrial, cytosolic, and membrane proteins.
In comparative analyses against healthy controls, the h-EV fraction revealed 86 proteins that were uniquely detected or significantly elevated in liver disease, reflecting shared pathways of fibrosis, disordered fat metabolism, and inflammation. In contrast, bulk EVs yielded four unique proteins and showed no significant differential signal. Furthermore, when comparing HCC directly with cirrhosis, the h-EV fraction resolved specific HCC-defining proteins and an interconnected protein network, neither of which could be resolved using paired bulk EVs.
Multiomic Profiling and Diagnostic Applications
Small-RNA sequencing provided additional validation across a second molecular layer. When comparing HCC with cirrhosis, the h-EV fraction produced fewer differentially expressed microRNAs than bulk EV preparations; however, only the microRNAs from the h-EV fraction mapped directly to HCC signaling pathways. MicroRNAs derived from bulk preparations mapped instead to generalized inflammatory responses. Because the same h-EVs were present in the bulk mixture, the authors noted that isolating tissue-specific vesicles can address the lack of biological specificity that has historically limited microRNAs as circulating biomarkers.
“Much of liquid biopsy has focused on measuring more analytes. Our thesis is that biological context matters as much as analytical depth. That is the foundation of EvoLiver and of the precision medicine programs we are building with pharma partners,” says Pierre Arsène, founder and CEO of Mursla Bio, in a release.
According to the company, the hepatocyte panel represents the first application of its TS-EV platform. The discovery and validation process is designed to expand to additional organs, with panels for other tissues currently in development. Potential clinical laboratory applications span disease surveillance, molecular residual disease monitoring, patient stratification, pharmacodynamic biomarker tracking, and companion diagnostics.
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