Abstract
Despite the high prevalence of liver disease globally, there are currently no approved anti-fibrotic therapies to treat patients with liver fibrosis. A major goal in anti-fibrotic therapy is the development of drug delivery systems that allow direct targeting of the major pro-scarring cell populations within the liver (hepatic myofibroblasts) whilst not perturbing the homeostatic functions of other mesenchymal cell types present within both the liver and other organ systems. In this review we will outline some of the recent advances in our understanding of myofibroblast biology, discussing both the origin of myofibroblasts and possible myofibroblast fates during hepatic fibrosis progression and resolution. We will then discuss the various strategies currently being employed to increase the precision with which we deliver potential anti-fibrotic therapies to patients with liver fibrosis.
Highlights
Liver disease is an increasing cause of morbidity and mortality worldwide
Given the negative charge associated with the mannose 6-phosphate carrier, it has been suggested that they could be a target for scavenger receptors such as those found on Kupffer cells and endothelial cells[28]
It is likely that hepatic stellate cell (HSC) are a major contributor to the myofibroblast population, it is important that we continue to delve into the pool of cells giving rise to hepatic myofibroblasts, as further increasing our knowledge of the cellular and molecular mechanisms driving both hepatic fibrosis evolution and resolution will undoubtedly allow us to increase the potency and precision of new anti-fibrotic therapies
Summary
Liver disease is an increasing cause of morbidity and mortality worldwide. Recent data show that approximately 29 million people in the European Union suffer from a chronic liver condition[1]. Given the negative charge associated with the mannose 6-phosphate carrier, it has been suggested that they could be a target for scavenger receptors such as those found on Kupffer cells and endothelial cells[28] Another approach to HSC-specific drug delivery has involved the coupling of peptide-modified proteins designed to recognise specific receptors on the target cells. A more recent study has coupled adenovirus with a peptide showing affinity to the p75 neurotrophin receptor, which is present on HSCs and myofibroblasts[43,44] Using this construct, the authors were able to show that in vivo expression of certain transcription factors enabled the re-programming of myofibroblasts to hepatocyte-like cells in fibrotic mouse livers and reduced liver fibrosis[43]. The ability to target scar-producing cells within the liver and reprogramme them to become cells with a positive functional benefit has massive therapeutic potential
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call