Understanding the Mechanisms of Human Liver Regeneration via Characterization of Circulating Extracellular Vesicles

Aim Our study is aimed at identifying circulating extracellular vesicles associated with liver regeneration in humans and mice, exploring their roles, and evaluating their content as potential biomarkers of regeneration. Methods Plasma samples were collected from 12 human liver transplant recipients and 22 mice at distinct time points postsurgery, corresponding to regenerating and nonregenerating phases. Small extracellular vesicles were isolated from plasma, and miRNA was extracted for analysis using NanoString technology. To understand the role of miRNAs in liver regeneration, we utilized bioinformatics tools, including mirDIP and STRING, to identify target genes involved in regenerative signaling pathways, focusing on the Hippo and cell cycle pathways. Results Twenty‐five differentially expressed miRNAs were identified from human patient plasma samples and 30 from mouse plasma samples. Bioinformatic analysis revealed a significant overlap between the predicted target genes of these miRNAs and genes involved in critical regenerative pathways, such as the cell cycle and Hippo signaling, suggesting that these miRNAs play important regulatory roles during liver regeneration. Conclusions The miRNA profiles associated with small extracellular vesicles have the potential to serve as noninvasive biomarkers for liver regeneration. Further validation of these miRNA‐based biomarkers could advance diagnostic and therapeutic approaches for liver injury and posttransplant recovery.