Update on hepatic stellate cells: pathogenic role in liver fibrosis and novel isolation techniques

Abstract

Hepatic stellate cells (HSCs), also called Ito cells or lipocytes, are vitamin A-storing cells located in the Dissé space between hepatocytes and sinusoidal endothelial cells. Upon liver injury, these cells transdifferentiate into extracellular matrix-producing, highly proliferative myofibroblasts that promote hepatic fibrogenesis. Other possible collagen-producing cells in liver fibrosis include portal fibroblasts, bone marrow-derived cells (mesenchymal stem cells, fibrocytes and hematopoietic cells) and parenchymal cells undergoing epithelial-to-mesenchymal transition. Important factors and signaling pathways for HSC activation, as well as different functions of HSC during homeostasis and fibrosis, such as collagen production, secretion of cytokines and chemokines, immune modulation and changes in contractile features, as well as vitamin A storage capacity, have been identified in vitro and in vivo. Novel isolation techniques, specifically HSC sorting by FACS via autofluorescence and antibodies, will provide us with further opportunities to advance our understanding of HSC biology in health and disease.

Keywords::

• collagen
• ECM
• FACS
• hepatic stellate cells
• HSC
• Kupffer cells
• liver fibrosis
• PDGF
• sorting
• TGF

Financial & competing interests disclosure

F Tacke and R Weiskirchen guide a central core facility for isolation of hepatic stellate cells using novel FACS-based technologies that is supported by a grant from the Deutsche Forschungsgemeinschaft (SFB/TRR57). The authors acknowledge the help of Carmen Tag and Sibille Sauer-Lehnen working in this facility and Dr Günther Hollweg (Institute of Pathology, RWTH University Aachen) for assistance in performing electron microscopy. The authors are indebted to all members of the Tacke and Weiskirchen labs and to our collaborating groups in the SFB/TRR57 for helpful discussions. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.