Targeting activated hepatic stellate cells (aHSCs) for liver fibrosis imaging.

Dan Li,Li He,Hong Shan,Hanwei Chen,Huizhuang Guo

doi:10.1186/s13550-015-0151-x

Abstract

Following injurious stimuli, quiescent hepatic stellate cells (qHSCs) transdifferentiate into activated HSCs (aHSCs). aHSCs play pivotal roles in the onset and progression of liver fibrosis. Therefore, molecular imaging of aHSCs in liver fibrosis will facilitate early diagnosis, prognosis prediction, and instruction and evaluation of aHSC-targeted treatment. To date, several receptors, such as integrin αvβ3, mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-IIR), collagen type VI receptor (CVIR), platelet-derived growth factor receptor-β (PDGFR-β), vimentin, and desmin, have been identified as biomarkers of aHSCs. Corresponding ligands to these receptors have also been developed. This review will discuss strategies for developing aHSC-targeted imaging in liver fibrosis.

Highlights

Liver fibrosis is a major public health problem and contributes to substantial morbidity and mortality
Abnormal wound healing processes, and redundant extracellular matrix (ECM) accumulation lead to liver fibrosis
We summarize recent studies on activated hepatic stellate cell-targeted imaging in liver fibrosis

Summary

Introduction

Liver fibrosis is a major public health problem and contributes to substantial morbidity and mortality. Studies in liver fibrosis show that integrin αvβ is upregulated on aHSCs [44,45,46] and promotes HSCs survival and proliferation [44]. The modified peptide is cyclized through an amide linkage between the cysteine and lysine residues and is more stable This peptide was conjugated to liposomes for aHSC-targeted drug delivery in liver fibrosis [98, 99]. Serum albumin-based carriers (M6P21-BSA, pCVI-HSA, pPBHSA) preferentially targeted HSCs in fibrotic livers, they were uptaken by endothelial cells [75, 97] or hepatocytes [105] in normal livers. The accumulation level of these carriers in both fibrotic and normal livers was similar [75, 97, 105] This characteristic makes these carriers suitable for HSC-targeted drug delivery rather than imaging. Tumor-derived factors activate HSCs, and in turn, aHSCs promote phenotypic changes, proliferation, and invasion of tumor

Biomarker Ligand

Findings

Conclusions