Development Service of Exovesicles (EVs) Markers

As the gold standard procedure to distinguish non-alcoholic fatty liver disease (NAFLD)/Nonalcoholic steatohepatitis (NASH), liver fibrosis lacks required sensitivity and specificity for early stages of fibrosis and is not useful for determination of inflammation and hepatocellular injury. This limitation has resulted in the study of novel circulating markers as potential candidates, among which, one of the most popular indicators are extracellular vesicles (EVs). Creative Biolabs now offers one-stop development services of EVs biomarkers for non-invasive diagnosis of NASH.

Introduction of Extracellular Vesicles

Exovesicles (extracellular vesicles, EVs) are small membrane vesicles that are released from damaged or activated cells in a highly regulated manner, with a subclass of three membrane-bound structures (exosomes, ectosomes, apoptotic bodies) based on their size, typical markers, and biogenesis. EVs have been identified as effective intercellular messengers that transfer several biologically active molecules to target cells, modulating the pathogenesis and progression of NASH. Cells respond to various stimuli that cause inflammation and metabolic stress, leading to their activation, impaired function or apoptosis. This mechanism drives the release of the EVs, which signals the paracrine or distal effector to the condition of the cellular microenvironment. In turn, effector cells can respond through small regulatory nucleic acids (mRNA and miRNA), lipids and proteins contained in the EV that selectively confer uptake by the recipient cells. The EV subclasses are identified by membrane labeling, which indicates the site of its biogenesis. In the course of lipotoxicity, hepatocytes release large amounts of EVs to act on various target cells in the local environment, which contributes to key processes involved in the pathogenesis of NAFLD, including angiogenesis, fibrosis, and inflammation.

Fig.1 Hepatocyte-derived EVs contribute to the progression of fatty liver diseases. (Eguchi, 2018)

Biomarkers of EVs for NASH Diagnosis

Based on the biogenesis and composition, EVs play a key pathophysiological role in liver injury and can be identified as novel non-invasive and reliable biomarkers for liver injury during NASH development. The miRNAs encapsulated in circulating EVs are increasingly showing great potential for achieving several criteria of good biomarkers, such as specificity, sensitivity, robustness, predictability, translatability, and non-invasiveness. Circulating EVs isolated from NASH are rich in miR-122 and miR-192, and both microRNAs are abundantly expressed in the liver. During the progression of NAFLD, the levels of these microRNAs are increased in EVs and decreased in the liver because they are released from stressed or damaged hepatocytes to EVs. Therefore, the EVs can be released into the systemic circulation and can potentially be used to non-invasively monitor the extent of liver damage.

Fig.2 Characterization of EVs. (Povero, 2016)

EVs are secreted from stressed and activated cells or are formed during apoptosis, and they are known to be involved in intercellular communication. The role of EVs in immunity and epigenetic regulation is widely attested, and their correlation with disease severity has been demonstrated, making these structures an advantageous target for diagnosis and treatment. In order to improve the value of these diagnostic tools and help clinicians in the diagnosis, prognosis, and staging of NASH, Creative Biolabs provides customized services (e.g. Phage Display & Antibody Library, Antibody Analysis, Antibody Engineering) to produce high-quality biomarkers for NASH non-intrusive diagnosis. If you have any special needs in NASH services, please feel free to contact us for more details.

References

1. Eguchi, A.; Feldstein, A.E. Extracellular vesicles in non-alcoholic and alcoholic fatty liver diseases. Liver research. 2018, 2(1): 30-34.
2. Povero, D.; Feldstein, A.E. Novel molecular mechanisms in the development of non-alcoholic steatohepatitis. Diabetes & metabolism journal. 2016, 40(1): 1-11.